Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. ...Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. Key target genes are involved in crucial cellular events such as DNA repair, cell cycle regulation, apoptosis, metabolism, and senescence. TP53 genetic variants and the activity of the wild-type p53 protein (WT-p53) have been linked to a wide range of tumorigenesis. Various genetic and epigenetic alterations, including germline and somatic mutations, loss of heterozygosity, and DNA methylation, can alter TP53 activity, potentially resulting in cancer initiation and progression. This study was designed to screen three reported mutations in the DNA-binding domain of the p53 protein in breast cancer, to evaluate the relative susceptibility and risk associated with breast cancer in the local population. Genomic DNA was isolated from 30 breast tumor tissues along with controls. Tetra and Tri ARMS PCR were performed to detect mutations in the TP53 coding region. For SNPs c.637C>T and c.733C>T, all analyzed cases were homozygous for the wild-type allele ‘C,’ while for SNP c.745A>G, all cases were homozygous for the wild-type allele ‘A.’ These results indicate no relevance of these three SNPs to cancer progression in our study cohort. Additionally, the findings from whole exon sequencing will help to predict more precise outcomes and assess the importance of TP53 gene mutations in breast cancer patients.展开更多
In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrho...In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.展开更多
AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study t...AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis,proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30H. Pylori-negative and 30 H. Pylorf-positive gastric precancerous lesions along with 20 gastric carcinomas were studied.RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (Al, 4.36% ± 1.95%), proliferative index (PI, 19.11% ± 6.79%) and positivity of p53 expression (46.7%) in H. Pylori-positive group were higher than those in normal mucosa (P< 0.01). Al in H. Pylori-positive group was higher than that in H. Pylori-negative group (3.81% ±1.76%), PI in H. Pylori-positive group was higher than that in H. Pylori-negative group (12.25% ±5.63%, P<0.01 ). In the phase of dysplasia, Al (2.31% ± 1.10%) in H. Pylori-positive group was lower (3.05% ± 1.29%) than that in H. Pylori-negative group, but PI (33.89% ± 11.65%)wassignificantly higher(22.09± 8018%, P< 0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. Pylori-positive group, Als had an evidently graduall decreasing trend (P < 0.01 ), while Pis had an evidently gradual increasing trend (P< 0.05 or P< 0.01), and there was also a trend of gradual increase in the expression of p53 gene.CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. Pylori, and H. Pylori can induce apoptosis in the phase of metaplasia but in the phase of dysplasia H.pylori can inhibit cellular apoptosis. And H. Pylori infection can strengthen the expression of mutated p53 gene.展开更多
INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced b...INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).展开更多
INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poo...INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poor prognosis.In recent decade,the incidence of adenocarcinoma of gastric eardiaand esophagus are increasing steadily,while therehas been a decrease in the proportion of the cancersarising from the distal stomach.The展开更多
p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results sho...p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37. 5 % (3/8), 42. 11 % (8/19), 53. 33 (16/30) respectively- There was significant dif-ference among groups of metaplasia, dysplasia, cancer and normal controls. Noexon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course ofprecancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,APC was 47,37 % (9/19), 8. 73% (2/23), 16. 67 % (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis,depth of invasion- LOH of exon4 may be one of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric carcinogenesis展开更多
Cisplatin damages cochlear hair cells and spiral ganglion neurons through cell death signaling pathways that are not fully understood. We used focused apoptosis gene microarrays to study early changes in gene expres- ...Cisplatin damages cochlear hair cells and spiral ganglion neurons through cell death signaling pathways that are not fully understood. We used focused apoptosis gene microarrays to study early changes in gene expres- sion in cochlear cultures from P3 neonatal rats treated with cisplatin (0.2 mM). After 12 hours of cisplatin treat- ment, more than 50% of the 96 genes on the array showed a significant decrease in expression, consistent with widespread cell death. However, after 3 hours of cisplatin treatment, 10 genes showed significant increase in ex- pression in total cochlear tissue. In experiments with subsets of cochlear tissues, at 3h, cisplatin induced increased expression of 12 genes in the cochlear sensory epithelium (basilar membrane) and 11 genes in the spiral ganglion (tissue of Rosenthal’s canal, containing the spiral ganglion). These included pro- and anti-apoptotic genes in- volved in the p53 signaling pathway, TNF receptor family, NF-kappaB pathway, death domain family, death effec- tor domain family, Bcl-2 family, CARD family, TRAF family, and GTP signal transduction. Although the changes in gene expression showed an overlap between basilar membrane and spiral ganglion, other changes, which may reflect the unique response of each tissue, were also observed. Pifithrin-α blocked cisplatin-induced up-regulation of genes in the p53 signaling pathway when assayed by both superarray and real time PCR. The data add to our understanding of the involvement of p53 in cisplatin-induced ototoxicity and otoprotection, conferred by the p53 inhibitor Pifithrin-α.展开更多
To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on ch...To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular展开更多
Objective: To evaluate the effect of adenovirus-mediated p53 gene (Adp53) on apoptosis andradiosensitivity of human gastric carcinoma cell lines.Methods: Recombinant adenovirus expressing wild-type p53 gene was transf...Objective: To evaluate the effect of adenovirus-mediated p53 gene (Adp53) on apoptosis andradiosensitivity of human gastric carcinoma cell lines.Methods: Recombinant adenovirus expressing wild-type p53 gene was transferred into four human gastric carcinoma cell lines with different p53 genetic status. p53 proteinexpression was detected by immunohistochemistry assayand western blot assay. Cell survival was assessed using a clonogenic assay. TUNEL assay was used in determination of apoptosis. Four human gastric carcinoma cells infectedwith Adp53 were irradiated with 4Gy and cell cycle distribution and Sub-G1 peak were assayed by flowcytometry. Results: G2/M arrest, apoptosis and inhibition of tumor cell proliferation were induced by infection atAdp53 at 100 MOI which caused high transfer rate ofwild-type p53 and strong expression of p53 protein in four human gastric carcinoma cells. The radio-enhancement ratio of Adp53 at 4Gy were 3.0 for W cell, 3.6 for M cell, 2.2 for neo cell and 2.5 for 823 cell in vitro. Conclusion: Thisstudy demonstrated that Adp53 transfer increased cellularapoptosis and radiosensitivity of human gastric carcinoma cell lines in vitro independently on cellular intrinsic p53status thus supporting the combination of p53 gene therapy with radiotherapy in clinical trials.展开更多
Objective: To explore the changes and significance of tumor suppressor gene p53 in primary hepatocellu-lar carcinoma (PHC ) with hepatitis B virus (HBV ) infection. Methods: Tumor tissues and surrounding nontumortissu...Objective: To explore the changes and significance of tumor suppressor gene p53 in primary hepatocellu-lar carcinoma (PHC ) with hepatitis B virus (HBV ) infection. Methods: Tumor tissues and surrounding nontumortissues of sixteen PHC cases were studied by Southern hybridization to detect the state of HBV-DNA in tissues, byimmunohistochemical staining to determine HBsAg, HBxAg and p53 protein, and by PCR directed sequencing toanalyse the point mutation of p53 gene exons 5 to 8. Results: Among the 16 cases. 13 cases were HBV-DNA posi-tive, 10 tumor cases and 13 nontumor tissues cases HBxAg positive, and 9 cases posltive for p53 protein. The se-quencing of p53 gene point mutation was found in 5 cases, only one of which was sited at codon 249 G to T. Con-clusion: The mutation of p53 gene codon 249 is infrequent in HBV related PHC,indicating the accumulation of p53protein in cells may be associated with expression of HBxAg. HBxAg binding to p53 protein and inactivation of p53function play important roles in the development of PHC.展开更多
文摘Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. Key target genes are involved in crucial cellular events such as DNA repair, cell cycle regulation, apoptosis, metabolism, and senescence. TP53 genetic variants and the activity of the wild-type p53 protein (WT-p53) have been linked to a wide range of tumorigenesis. Various genetic and epigenetic alterations, including germline and somatic mutations, loss of heterozygosity, and DNA methylation, can alter TP53 activity, potentially resulting in cancer initiation and progression. This study was designed to screen three reported mutations in the DNA-binding domain of the p53 protein in breast cancer, to evaluate the relative susceptibility and risk associated with breast cancer in the local population. Genomic DNA was isolated from 30 breast tumor tissues along with controls. Tetra and Tri ARMS PCR were performed to detect mutations in the TP53 coding region. For SNPs c.637C>T and c.733C>T, all analyzed cases were homozygous for the wild-type allele ‘C,’ while for SNP c.745A>G, all cases were homozygous for the wild-type allele ‘A.’ These results indicate no relevance of these three SNPs to cancer progression in our study cohort. Additionally, the findings from whole exon sequencing will help to predict more precise outcomes and assess the importance of TP53 gene mutations in breast cancer patients.
文摘In the world,hepatocellular carcinoma(HCC)is among the top 10 most prevalent malignancies.HCC formation has indeed been linked to numerous etiological factors,including alcohol usage,hepatitis viruses and liver cirrhosis.Among the most prevalent defects in a wide range of tumours,notably HCC,is the silencing of the p53 tumour suppressor gene.The control of the cell cycle and the preservation of gene function are both critically important functions of p53.In order to pinpoint the core mechanisms of HCC and find more efficient treatments,molecular research employing HCC tissues has been the main focus.Stimulated p53 triggers necessary reactions that achieve cell cycle arrest,genetic stability,DNA repair and the elimination of DNA-damaged cells’responses to biological stressors(like oncogenes or DNA damage).To the contrary hand,the oncogene protein of the murine double minute 2(MDM2)is a significant biological inhibitor of p53.MDM2 causes p53 protein degradation,which in turn adversely controls p53 function.Despite carrying wt-p53,the majority of HCCs show abnormalities in the p53-expressed apoptotic pathway.High p53 in-vivo expression might have two clinical impacts on HCC:(1)Increased levels of exogenous p53 protein cause tumour cells to undergo apoptosis by preventing cell growth through a number of biological pathways;and(2)Exogenous p53 makes HCC susceptible to various anticancer drugs.This review describes the functions and primary mechanisms of p53 in pathological mechanism,chemoresistance and therapeutic mechanisms of HCC.
基金Supported by National Ninth Five-Year Study Program for Tacking Key Scientific Problems.No.96-906-01-04
文摘AIM: To study the relationship between Helicobacter pylori (H. Pylori) and gastric carcinoma and its possible pathogenesis by H. Pylori.METHODS: DNEL technique and immunohistochemical technique were used to study the state of apoptosis,proliferation and p53 gene expression. A total of 100 gastric mucosal biopsy specimens, including 20 normal mucosa, 30H. Pylori-negative and 30 H. Pylorf-positive gastric precancerous lesions along with 20 gastric carcinomas were studied.RESULTS: There were several apoptotic cells in the superficial epithelium and a few proliferative cells within the neck of gastric glands, and no p53 protein expression in normal mucosa. In gastric carcinoma, there were few apoptotic cells, while there were a large number of proliferative cells, and expression of p53 protein significantly was increased. In the phase of metaplasia, the apoptotic index (Al, 4.36% ± 1.95%), proliferative index (PI, 19.11% ± 6.79%) and positivity of p53 expression (46.7%) in H. Pylori-positive group were higher than those in normal mucosa (P< 0.01). Al in H. Pylori-positive group was higher than that in H. Pylori-negative group (3.81% ±1.76%), PI in H. Pylori-positive group was higher than that in H. Pylori-negative group (12.25% ±5.63%, P<0.01 ). In the phase of dysplasia, Al (2.31% ± 1.10%) in H. Pylori-positive group was lower (3.05% ± 1.29%) than that in H. Pylori-negative group, but PI (33.89% ± 11.65%)wassignificantly higher(22.09± 8018%, P< 0.01). In phases of metaplasia, dysplasia and gastric cancer in the H. Pylori-positive group, Als had an evidently graduall decreasing trend (P < 0.01 ), while Pis had an evidently gradual increasing trend (P< 0.05 or P< 0.01), and there was also a trend of gradual increase in the expression of p53 gene.CONCLUSION: In the course of the formation of gastric carcinoma, proliferation of gastric mucosa can be greatly increased by H. Pylori, and H. Pylori can induce apoptosis in the phase of metaplasia but in the phase of dysplasia H.pylori can inhibit cellular apoptosis. And H. Pylori infection can strengthen the expression of mutated p53 gene.
基金the National Natural Science Foundation of China,No.39260033.
文摘INTRODUCTIONIn order to study the relationship between oncogeneexpression and HCC generation,we observed theprecancerous hepatic GGT loci,IGF-Ⅱ,p53 andp21 expression during hepatocarcinogenesis of treeshrew induced by hepatitis B virus (HBV) and/oraflatoxin B1 (AFB1).
文摘INTRODUCTIONAdenocarcinomas of the cardia are the lesionsarising from the proximal stomach or within 3 cm ofthe gastroesophageal junction.These cancerstended to be advanced at the time of presentation,usually with poor prognosis.In recent decade,the incidence of adenocarcinoma of gastric eardiaand esophagus are increasing steadily,while therehas been a decrease in the proportion of the cancersarising from the distal stomach.The
文摘p53 gene mutation (exon4, 5, 6, 7, 8 and intron6) in gastric cancer and precancerous lesions and p53 gene (exon4 and ontron6), APC gene deletion in gastric carcinomas were studied by PCR/SSCP and PCR/RFLP- Results showed mutation rate of p53 in metaplasia, dysplasia and gastric carcinoma was 37. 5 % (3/8), 42. 11 % (8/19), 53. 33 (16/30) respectively- There was significant dif-ference among groups of metaplasia, dysplasia, cancer and normal controls. Noexon8 mutation was found in metaplasia and dysplasia, but 4 cases were found to have exon8 mutation in cancer group. It is suggested that exon8 mutation occurs at the late stage of gastric cancer, but exon 5, 6, 7 mutation occur in the course ofprecancerous lesion to cancer. Loss of heterozygosity (LOH) of exon4, intron6,APC was 47,37 % (9/19), 8. 73% (2/23), 16. 67 % (3/18) respectively. LOH of exon4 had something to do with poor differentiation, lymph node metastasis,depth of invasion- LOH of exon4 may be one of prognostic marker of gastric cancer. We are led to conclude that p53 gene mutation is an early event and perhaps work together with ras oncogene in gastric carcinogenesis
文摘Cisplatin damages cochlear hair cells and spiral ganglion neurons through cell death signaling pathways that are not fully understood. We used focused apoptosis gene microarrays to study early changes in gene expres- sion in cochlear cultures from P3 neonatal rats treated with cisplatin (0.2 mM). After 12 hours of cisplatin treat- ment, more than 50% of the 96 genes on the array showed a significant decrease in expression, consistent with widespread cell death. However, after 3 hours of cisplatin treatment, 10 genes showed significant increase in ex- pression in total cochlear tissue. In experiments with subsets of cochlear tissues, at 3h, cisplatin induced increased expression of 12 genes in the cochlear sensory epithelium (basilar membrane) and 11 genes in the spiral ganglion (tissue of Rosenthal’s canal, containing the spiral ganglion). These included pro- and anti-apoptotic genes in- volved in the p53 signaling pathway, TNF receptor family, NF-kappaB pathway, death domain family, death effec- tor domain family, Bcl-2 family, CARD family, TRAF family, and GTP signal transduction. Although the changes in gene expression showed an overlap between basilar membrane and spiral ganglion, other changes, which may reflect the unique response of each tissue, were also observed. Pifithrin-α blocked cisplatin-induced up-regulation of genes in the p53 signaling pathway when assayed by both superarray and real time PCR. The data add to our understanding of the involvement of p53 in cisplatin-induced ototoxicity and otoprotection, conferred by the p53 inhibitor Pifithrin-α.
基金supported by the Chinese High-Tech Program(863)Chinese Key Basic Research Project(973)the National Natural Science Foundation of China.Gratitude was extended to Prof.Zhu CHEN for his suggestion and direction of this work.
文摘To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular
基金This work was supported by the National Natural Foundation of China (No. 39670234 )
文摘Objective: To evaluate the effect of adenovirus-mediated p53 gene (Adp53) on apoptosis andradiosensitivity of human gastric carcinoma cell lines.Methods: Recombinant adenovirus expressing wild-type p53 gene was transferred into four human gastric carcinoma cell lines with different p53 genetic status. p53 proteinexpression was detected by immunohistochemistry assayand western blot assay. Cell survival was assessed using a clonogenic assay. TUNEL assay was used in determination of apoptosis. Four human gastric carcinoma cells infectedwith Adp53 were irradiated with 4Gy and cell cycle distribution and Sub-G1 peak were assayed by flowcytometry. Results: G2/M arrest, apoptosis and inhibition of tumor cell proliferation were induced by infection atAdp53 at 100 MOI which caused high transfer rate ofwild-type p53 and strong expression of p53 protein in four human gastric carcinoma cells. The radio-enhancement ratio of Adp53 at 4Gy were 3.0 for W cell, 3.6 for M cell, 2.2 for neo cell and 2.5 for 823 cell in vitro. Conclusion: Thisstudy demonstrated that Adp53 transfer increased cellularapoptosis and radiosensitivity of human gastric carcinoma cell lines in vitro independently on cellular intrinsic p53status thus supporting the combination of p53 gene therapy with radiotherapy in clinical trials.
文摘Objective: To explore the changes and significance of tumor suppressor gene p53 in primary hepatocellu-lar carcinoma (PHC ) with hepatitis B virus (HBV ) infection. Methods: Tumor tissues and surrounding nontumortissues of sixteen PHC cases were studied by Southern hybridization to detect the state of HBV-DNA in tissues, byimmunohistochemical staining to determine HBsAg, HBxAg and p53 protein, and by PCR directed sequencing toanalyse the point mutation of p53 gene exons 5 to 8. Results: Among the 16 cases. 13 cases were HBV-DNA posi-tive, 10 tumor cases and 13 nontumor tissues cases HBxAg positive, and 9 cases posltive for p53 protein. The se-quencing of p53 gene point mutation was found in 5 cases, only one of which was sited at codon 249 G to T. Con-clusion: The mutation of p53 gene codon 249 is infrequent in HBV related PHC,indicating the accumulation of p53protein in cells may be associated with expression of HBxAg. HBxAg binding to p53 protein and inactivation of p53function play important roles in the development of PHC.
