Differential expression of breast cancer-resistance protein,lung resistance protein,and multidrug resistance protein 1 in retinas of streptozotocin-induced diabetic mice

AIM：To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein（BCRP）,lung resistance protein（LRP）,and multidrug resistance protein 1（MDR1） at the inner blood-retinal barrier（BRB） during the development of early diabetic retinopathy（DR） and/or aging in mice.METHODS：Relative m RNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined.The differing expression profiles of Zonula occludens 1（ ZO-1） and vascular endothelial growth factor-A（ VEGFA） in the retina as well as the perfusion characterization of fluorescein isothiocyanate（FITC）-dextran and Evans blue were examined to evaluate the integrity of the inner BRB.RESULTS：There were significant alterations in these three efflux transporters＇ expression profiles in the m RNA and protein levels of the retina during the development of diabetes mellitus and/or aging.The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.CONCLUSION：The expression profiles of some efflux transporters such as BCRP,LRP,and MDR1 in mice retina during diabetic and/or aging conditions are tested,and the attenuated expression of BCRP,LRP,and MDR1 along with the breakdown of the inner BRB is found,which may be linked to the pathogenesis of early DR.

Molecular Docking Studies of Botanical Beverage Mix Berries (LIFEGREENTM) against Breast Cancer Cells from Targeted Protein 1QQG, 7B5Q & 7B5O & Uterine Fibroid from Targeted Protein 2AYR, 6T41 & 3GRF

Fibroids, also called leiomyomas or myomas, are communal tumors of the muscle or uterine wall that affect about 20% of females who are of reproductive age. They can look as if singly or in clusters, and they often cease to grow after menopause. Fibroids can be classified as intramural, sub serosal, pedunculated, or submucosal based on where they are positioned in the uterus. Although fibroids are benign, they can grow quickly and cause a range of symptoms, such as pelvic pressure, heavy menstrual flow, and infertility. As a result, fibroids are a main reason behind hysterectomy surgeries. The majority of cases of breast cancer are ductal and lobular cancers, making it the second utmost common cancer in women international. Gene mutations like those in BRCA1 or BRCA2 knowingly raise the risk of breast and other cancers, typically with an earlier cancer onset. Cancer risk is influenced by a complex interplay of genetic abnormalities, environmental factors, and lifestyle selections. Further research into these relations is domineering. Although they are common in uterine leiomyomas, especially multiple leiomyomas, MED12 mutations do not significantly correlate with tumor size. These mutations have also been noticed in smooth muscle tumors and leiomyosarcomas, two other types of uterine cancer. The identification of MED12 mutations as the sole genetic abnormality originates in leiomyomas raises the opportunity of a role in the genesis of cancer. 10% - 15% of women who are of reproductive age have endometriosis, which grants serious difficulties because of its chronic nature and range of clinical symptoms. Even after effective surgeries, issues reoccur often, adding to the enormous financial burden. The effects of MED12 mutations have been experiential in recent studies examining the molecular causes of endometriosis-associated infertility, which have shown anomalies in cellular connections and signaling cascades. Computational techniques were used in this study to investigate LifeGreenTM’s potential to prevent uterine fibroids and breast cancer. The efficacy of LifeGreenTM as a preventive measure or a treatment for common gynecological matters was examined and modeled. We investigated the mechanisms underlying LifeGreenTM’s benefits in the treatment of uterine fibroids and breast cancer using computational techniques. Our research contributes to our understanding of its potential therapeutic benefits for women’s health.

Breast Cancer Resistance Protein Expression and 5-Fluorouracil Resistance

Objective To filtrate breast cancer resistance protein （BCRP）-mediated resistant agents and to investigate clinical relationship between BCRP expression and drug resistance. Methods MTT assay was performed to filtrate BCRP-mediated resistant agents with BCRP expression cell model and to detect chemosensitivity of breast cancer tissue specimens to these agents. A high performance liquid chromatography （HPLC） assay was established, and was used to measure the relative dose of intracellular retention resistant agents. RT-PCR and immunohistochemistry （IHC） were employed to investigate the BCRP expression in breast cancer tissue specimens. Results MTT assay showed that the expression of BCRP increased with the increasing resistance of 5-fluorouracil （5-Fu） （P〈0.05, n=3） in the cell model, while HPLC assay indicated that the intracellular retention dose of 5-Fu was significantly correlated with the expression of BCRP （t=-0.897, P〈0.05, n=3）. A total of 140 breast cancer tissue specimens were collected. BCRP-positive expression was detected in forty-seven specimens by both RT-PCR and IHC. As shown by MTT assay subsequently, the resistance index （RI） of 47 BCRP-positive breast cancer tissue specimens to 5-Fu was 7-12 times as high as that of adjacent normal tissue samples. BCRP expression was related to 5-Fu resistance （R2=0.8124, P〈0.01）. Conclusion Resistance to 5-Fu can be mediated by BCRR Clinical chemotherapy for breast cancer patients can be optimized based on BCRP-positive expression.

Effect of Ursolic Acid on Breast Cancer Resistance Protein-mediated Transport of Rosuvastatin In Vivo and Vitro

Objective To evaluate whether ursolic acid can inhibit breast cancer resistance protein(BCRP)-mediated transport of rosuvastatin in vivo and in vitro. Methods Firstly, we explored the pharmacokinetics of 5-fluorouracil(5-FU, a substrate of BCRP) in rats in the presence or absence of ursolic acid. Secondly, we studied the pharmacokinetics of rosuvastatin in rats in the presence or absence of ursolic acid or Ko143(inhibitor of BCRP). Finially, the concentration-dependent transport of rosuvastatin and the inhibitory effects of ursolic acid and Ko143 were examined in Madin-Darby Canine Kidney(MDCK) Ⅱ-BCRP421CC(wild type) cells and MDCKⅡ-BCRP421AA(mutant type) cells. Results As a result, significant changes in pharmacokinetics parameters of 5-FU were observed in rats following pretreatment with ursolic acid. Both ursolic acid and Ko143 could significantly affect the pharmacokinetics of rosuvastatin. The rosuvastatin transport in the BCRP overexpressing system was increased in a concentration-dependent manner. However, there was no statistical difference in BCRP-mediated transport of rosuvastatin betweent the wild type cells and mutant cells. The same as Ko143, ursolic acid inhibited BCRP-mediated transport of rosuvastatin in vitro. Conclusion Ursolic acid appears to be a potent modulator of BCRP that affects the pharmacokinetic of rosuvastatin in vivo and inhibits the transport of rosuvastatin in vitro.

Discovery of a small-molecule bromodomain-containing protein 4 inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer

OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy.

Combination immunotherapy with Survivin and luteinizing hormone-releasing hormone fusion protein in murine breast cancer model

AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.

Serum Y-Box Binding Protein 1 (YBX-1) and Interleukin 6 (IL-6) Are Associated with Metastasis in Breast Cancer Patients

Objectives: The aim of this study was to assess the levels of Y-box binding protein 1 (YBX-1) and interleukin 6 (IL-6) in the sera of metastatic and non-metastatic breast cancer patients (BC), investigate their clinicopathological significance and to analyze their potential use as biomarkers of breast cancer metastasis. Methods: The study included ninety subjects sub-grouped equally into metastatic BC, non-metastatic BC and healthy volunteers. Serum YBX-1 and IL-6 were quantified using ELISA technique while CA 15-3 was quantified using IRMA kit. Clinical data were collected from patients’ records. Results: YBX-1 (p < 0.001), IL-6 (p < 0.001) and CA15-3 (p = 0.017, 0.001) were significantly elevated in metastatic and non-metastatic BC patients compared to healthy controls, however, only YBX-1 (p 0.001) showed a significant difference with cancer metastasis. Generally, YBX-1 and IL-6 were correlated with worse histological grade and late clinical stage in breast cancer patients and they were also associated with axillary lymph nodes involvement and positive vascular invasion in metastatic BC patients. Serum YBX-1 and IL-6 levels were positively correlated to each other (rs = 0.615, p < 0.001) and they showed high sensitivity and specificity compared to CA 15-3 (p < 0.001 and p = 0.004 for YBX-1 and IL-6 respectively) for predicting cancer metastasis. Conclusions: Serum YBX-1 and IL-6 are potential biomarkers of breast cancer patients with significant correlation with bad clinicopathological characteristics. Serum YBX-1 and IL-6 have superior sensitivity and specificity compared to CA15-3 and can serve as potential follow up and prognostic markers.

Overexpression of centromere protein H is significantly associated with breast cancer progression and overall patient survival

Breast cancer is one of the leading causes of cancer death worldwide.This study aimed to analyze the expression of centromere protein H(CENP-H) in breast cancer and to correlate it with clinicopathologic data,including patient survival.Using reverse transcription-polymerase chain reaction and Western blotting to detect the expression of CENP-H in normal mammary epithelial cells,immortalized mammary epithelial cell lines,and breast cancer cell lines,we observed that the mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in immortalized mammary epithelial cells than in normal mammary epithelial cells.We next examined CENP-H expression in 307 paraffin-embedded archived samples of clinicopathologically characterized breast cancer using immunohistochemistry,and detected high CENP-H expression in 134(43.6%) samples.Statistical analysis showed that CENP-H expression was related with clinical stage(P = 0.001),T classification(P = 0.032),N classification(P = 0.018),and Ki-67(P < 0.001).Patients with high CENP-H expression had short overall survival.Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient survival.Our results suggest that CENP-H protein is a valuable marker of breast cancer progression and prognosis.

Differential Expressing of Centromere Protein CenpG in Breast Cancer

Using indirect immunofluorescence (IIF), an anti-centromere protein CenpG-serum was verified. Western blot of the protein extracts of 31 samples of breast cancer tissues and their normal (not cancerous ) tissues a little far away from them in the same individuals showed that, in the majority of the tests (71%), centromere protein CenpG over expressed in breast cancer tissues. And moreover, a kind of protein component whose molecular weight is 43 kd, and which can be recognized by anti-CenpG serum was found in two of the cancer samples. The results suggested that CenpG (together whith it, there may be other relative components),which has been found and named recently, may be related to cancer,and its differential expressing is probably related to malignant cell proliferation.

RELATIONSHIP AMONG PS_2 PROTEIN EXPRESSION, ESTROGENAND PROGESTERONE RECEPTOR STATUS, ANDPROGNOSIS OF BREAST CANCER

Objective: To study the relationship between theexpression of PS, protein and Estrogen (ER) andProgesterone Receptor (PR) status and their prognoticvalue in breast canceL Methods: Using theimmunohistochemical method, PS2 protein expressionswere detected in 105 cases with breast cancer. Results:The positive rate of PS2 protein was 50.48% (53/105) in105 cases. The positive rate of PS, in the patients whosurvived five years or more was 56.96% (45/79), whichwas higher than that of those who lived less than fiveyears (30.77%, 8/26). In the ER, PR (+) patients, thepositive rate of PS, was higher (76.74%, 33/34), thanthat of those with ER, PR (-) (22.5%, 9/40). Conclusions:Our results suggest that the expression of PS, proteinwas positively correlated with the 5-year-survival andthat of ER and PR in breast cancer. It is considered thatPS, may be as a prognostic predictor, and detection ofPS, protein expression was useful for a guidingtreatment of breast cancer.

Breast cancer and protein biomarkers

Breast cancer is a healthcare concern of women worldwide.Despite procedures being available for diagnosis,prognosis and treatment of breast cancer,researchers are working intensively on the disease in order to improve the life quality of breast cancer patients.At present,there is no single treatment known to bring a definite cure for breast cancer.One of the possible solutions for combating breast cancer is through identification of reliable protein biomarkers that can be effectively used for early detection,prognosis and treatments of the cancer.Therefore,the task of identification of biomarkers for breast cancer has become the focus of many researchers worldwide.

Breast and Ovarian Carcinoma Overexpress HLA-G, a Neglected Cancer Immunosuppressive Protein

Purpose: HLA-G binds to the inhibitory receptors of uterine NK cells and plays an important role in protection of fetal cells from maternal NK lysis. HLA-G also mediates tumor escape, but the immunosuppressive role is often neglected. These studies have focused on the examination of HLA-G expression in human breast and ovarian carcinoma and HLA-G immunosuppressive role in NK cytolysis. Methods: We examined HLA-G expression in breast and ovarian carcinoma cell lines by real time PCR, ELISA and immunofluorescent staining, and in frozen breast and ovarian carcinoma tissues by immunohistochemistry (IHC). We treated the breast cancer cell lines with anti-human HLA-G antibody or progesterone. Then, NK cytolysis was measured by using MTT assay. Results: We find breast and ovarian cancer cell lines increase the expression of HLA-G mRNA and protein, compared to normal cells. IHC shows that 100% of frozen breast and ovarian carcinoma tissues overexpress HLA-G protein. HLA-G IHC scores of breast and ovarian carcinoma are significantly higher than normal breast and ovarian tissues, respectively (both p < 0.01). Blocking HLA-G of the breast cancer cells by the antibody increases NK cytolysis. Progesterone upregulates HLA-G mRNA and protein of human breast cancer cell lines. The increased HLA-G expression by progesterone suppresses the NK cytolysis. Conclusion: Human breast and ovarian carcinoma overexpress HLA-G immunosuppressive molecules. Blocking HLA-G protein by antibody improves the cytolysis of NK cells against human breast cancer cell lines. In contrast, upregulation of HLA-G expression by progesterone impairs NK cytolytic function. Thus, HLA-G is a new immune checkpoint protein and potential cancer immunotherapeutic target.

Evaluation of the Dietary Reference Intakes for Japanese (2010 Edition): Recommended Protein, Pantothenic acid, Vitamin D, and Iron Intakes for Breast-Fed Infants Aged 6 - 11 Months

Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for every nutrient in actual dietary practice. Design: We evaluated (1) whether the DRIs for all nutrients can be fulfilled in a formula with energy and protein exceeding their DRIs, (2) whether the DRIs for all nutrients can be fulfilled in a formula prepared in accordance with Japanese government-recommended weaning guidelines, and (3) what kinds of formulas can be prepared if the DRIs for all nutrients are fulfilled without referring to the weaning guidelines. Setting: Simulation of diet menu on the basis of published data in our university and survey of diet menu in a university hospital attached to a national medical school. Subjects: The three types of formulas were planned for ten days. Results: It was impossible to simultaneously fulfil the DRIs for 6 - 8-month-old infants concerning pantothenic acid, vitamin D, and iron and those for 9 - 11-month-old infants concerning these nutrients plus protein. Conclusion: According to the DRIs-2010, the DRI for all nutrients could not be fulfilled in an ingestible formula.

Differential expression and clinical characteristics of Pim1 protein in different lesions of breast

Objective:To investigate the differential expression and clinical features of Pim1 protein in breast tissue of healthy people, mastitis and breast cancer patients.Methods:From September 2017 to September 2018, there were a blank group (39 normal residents), a mastitis group (39 mastitis patients), and a paracancerous tissue group (39 paracancerous tissues of breast cancer patients). Four groups of subjects in the adenocarcinoma group (39 breast cancer patients with breast cancer) were studied. To detect the difference of Pim1 protein expression levels in breast tissue of four groups of subjects, and analyze the effect of clinical condition on the expression of Pim1 protein in breast cancer patients.Results:Compared with the blank group, the difference of Pim1 protein expression between the mastitis group, the adenocarcinoma group and the paracancerous group was statistically significant. There was a statistically significant difference in Pim1 protein expression between the paracancerous tissue group and the adenocarcinoma tissue group. Pim1 protein expression is associated with lymph node metastasis, TNM stage, and ER expression in breast cancer patients, regardless of age, histological grade, PR, and Her-2. Pim1 protein expression was evaluated as a dependent variable in breast cancer patients. Lymph node metastasis, TNM staging, and ER were independent variables. The main factors affecting Pim1 protein expression in breast cancer patients were: ER expression (OR=4.759), lymph node metastasis (OR= 3.127), TNM staging (OR = 2.664).Conclusions: Pim1 protein is closely related to the occurrence and development of mastitis and breast cancer. The detection of this index can assess the status of breast inflammation and the risk of cancer in a certain degree, and it has certain reference value for early diagnosis of breast cancer.

Expression of MxA Protein in Triple Negative Breast Cancer and its Relationship with Prognosis

Objective:To explore the expression of human myxovirus resistance protein A(MxA)in triple negative breast cancer(TNBC)and its relationship with prognosis.Methods:144 cases of TNBC confirmed by pathology before or after surgery from January 2014 to January 2017 in the First Central Hospital of Baoding City were retrospectively collected.Western blotting was used to detect the expression of MxA protein in TNBC and adjacent breast tissues.According to the expression of MxA protein,144 TNBC patients were divided into low MxA protein expression group(n=91)and MxA protein high expression group(n=53)for subsequent comparison of prognosis of patients in between these two groups.Results:The expression of MxA protein in TNBC tissue was lower than that of adjacent breast tissue,and the difference was statistically significant(P<0.05).The patients in high MxA expression group had higher loco-regional recurrence-free rate,disease-free survival(DFS)rate,and overall survival(OS)rate than those in low MxA expression group for 3 years.On the other hand,the distant metastasis rate was lower in the high expression group compared to that in the low MxA expression group,and the difference was statistically significant(P<0.05).Conclusion:In triple-negative breast cancer,high MxA expression is a potential predictor of TNBC prognosis.

The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation

During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNAindependent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax(TrxG) and Polycomb(PcG) group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.

Research progress of TRIMs protein family in tumors

The tripartite motif(TRIMs)protein family has E3 ubiquitin ligase activity among most of its members.They participate in multiple cellular processes and signaling pathways in living organisms,including cell cycle,growth,and metabolism,and mediate chromatin modification,transcriptional regulation,post-translational modification,and cellular autophagy.Previous studies have confirmed that the TRIMs protein family is involved in the development of various cancers and correlated with the prognosis of tumor patients.Here we summarize the biological roles of the TRIMs protein family in cancers.

STUDY ON NUCLEAR MATRIX PROTEINS FROM HUMAN BREAST CARCINOMA

Objective To investigate the marker protein of human breast carcinoma from nuclear matrix proteins (NMPs). Methods NMPs were injected subcutaneously into rabbit to get antiserum, which was used to detect the NMPs specificity for breast carcinoma. Results There was an apparent positive band (100 kD) in the NMPs of breast carcinoma, which did not exist in normal breast and other tumors that were detected.Conclusion One or one group of 100 kD NMPs were found to be related to human breast carcinoma, which may be involved in the carcinogenesis and development of human breast carcinoma and valuable for breast carcinoma diagnosis.

High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer

BACKGROUND Breast cancer(BC) remains a public health problem. Tamoxifen(TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1(EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.AIM To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.METHODS High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.RESULTS EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.CONCLUSION This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

THE QUANTITATIVE MEASUREMENT OF BCL-2, P53 PROTEIN AND PCNA EXPRESSION IN BREAST CARCINOMA AND THEIR CORRELATION WITH PROGNOSIS

To study quantitative index of bci-2, P53, Nroliferating cell nuclear antigen (PCNA),ER and PR in breast carcinoma and their correiation and their relatiousbip with prognosis, the ex expression of bcl-2, P53 and PCNA were studied by immunohistochemical technique. The measurementof ER and PR used enzyme linked affinuity histochemical methods. The quantitative index was analyzed by image technique. All analyses were hased on 60 breast carcinomas. The results were as follows:the more bcl-2 protein, the lower histological graded the longer survival term and the highersurvival rate (P< 0. 05). The quautitative measurement of bcl-2, P53 and PCNA expression were ofvalue in evaluating the degree of differentiation and prognosis in breast carcinoma. The quantitativeand qualitative measurement or p53 protein expression showed a Ⅰwerful evidence in evaluatingprognosis of bcl-2 were more significant in evaluating poor prognosis of breast carcinoma. A relationship between bcl-2 and ER, PR showed a better value for response to endocrine therapy in breastcarcinoma patients.