p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-de...p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-degradation of p21Waf/Cip1, p16INK4a and p14ARF remain unclear. In this study, we showed enhanced expression of p21Waf/Cip1, p16INK4a and p19ARF in multiple tissues from REGg–/– mice compared to REGg+/+ mice. Furthermore, we examined the expression of p21Waf/Cip1, p16INK4a and p14ARF in different cancer tissues and observed that the REGγ protein levels were highly expressed in different human cancers while the level of p21Waf/Cip1, p16INK4a and p14ARF appears to be inversely correlated. These results demonstrate that REGγ may exert its function in physiological and pathological conditions through degradation of p21Waf/Cip1, p16INK4a and p14ARF in vivo.展开更多
This study examined the change of p16^INK4a and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts （hIG...This study examined the change of p16^INK4a and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts （hIGF-1-myoblasts） were injected into hind limb muscles of 18 post-infraction rats （experimental group）. Primary-myoblasts were injected into 18 post-infraction rats （control group） and 12 non-infarction rats （sham group）. Expression of p16INK4a and PCNA pro- tein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by en- zyme-linked immunosorbent assay （ELISA）. Compared with the sham group, the percentage of p^16INK4a and PCNA positive cells reached a peak after 1 week in the control group and the experimental group （P〈0.01）. Moreover, the percentage of p16^INK4a-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group （P〈0.01）. The percentage of p16^INK4a-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week （P〉0.05）. ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group （P〈0.01）. The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group （P〈0.01）. The hIGF-1 protein in serum and myocar- dium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p^16INK4a and PCNA protein （r=–0.323, P〈0.05; r=0.647, P〈0.01）. It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16^INK4a protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.展开更多
Aberrant expression of the cell cycle kinase inhibitors p16,p21,and p27has been associated with poor prognosis in a variety of human malignancies.Litt le is known,however,about their clinical impact in vulvar carcinom...Aberrant expression of the cell cycle kinase inhibitors p16,p21,and p27has been associated with poor prognosis in a variety of human malignancies.Litt le is known,however,about their clinical impact in vulvar carcinoma patients.Thus,we analyzed a larger series of v ulvar squamous cell carcinomas and compared the results with clinical outcome.A total of 224vulvar squamous cell carcinomas were im-munohistochemically investigated for expression of p16,p21,and p27using the biotin -strept avidin -peroxidase method and the OptiMax Plus automate d cell staining sys-tem.High p16(≥5%)positive nuclear immunostaining was found in 69(31%)cases,high p21(any staining)protein levels was detected in 95(42%)cases,and lowp27(≤50%positive nuclei)staining was seen in 170(76%)cases.High expression of p16was related to lower patient age and low expression of p53.High expression of p16indicated a better prognosis in t he multivariate analysis(RR =0.5,95%CI =0.2-1.0)and less risk of de-veloping lymph node metastasis(OR =0.3,95%CI =0.2-0.7).High level of p21was significantly associated with shorter survival in patients staged FIGO I and II(RR=3.4,95%CI =1.3-9.3).We found no significant correlation between the expression of p27and any of the clinicopathological variables.Our study indicates a prog-nostic relevance for p16and p21immu noreactivity.Low level of p16protein and high level of p21protein were as-sociated with a shorter disease -related survival.We did not find p27protein expression to be useful as a prognostic indicator in vulvar carcinoma patie nts.展开更多
文摘p21Waf/Cip1, p16INK4a and p14ARF (p19ARF in mice) have been demonstrated to be degraded by REGγ-proteasome pathway in an ATP- and ubiquitin-independent manner in vitro. However, the in vivo roles of REGγ mediated-degradation of p21Waf/Cip1, p16INK4a and p14ARF remain unclear. In this study, we showed enhanced expression of p21Waf/Cip1, p16INK4a and p19ARF in multiple tissues from REGg–/– mice compared to REGg+/+ mice. Furthermore, we examined the expression of p21Waf/Cip1, p16INK4a and p14ARF in different cancer tissues and observed that the REGγ protein levels were highly expressed in different human cancers while the level of p21Waf/Cip1, p16INK4a and p14ARF appears to be inversely correlated. These results demonstrate that REGγ may exert its function in physiological and pathological conditions through degradation of p21Waf/Cip1, p16INK4a and p14ARF in vivo.
基金the National Natural Sciences Foundation of China (No. 30470457)
文摘This study examined the change of p16^INK4a and PNCA protein expression in myocardium after injection of hIGF-1 gene modified skeletal myoblasts into post-infarction rats. HIGF-1 gene modified skeletal myoblasts （hIGF-1-myoblasts） were injected into hind limb muscles of 18 post-infraction rats （experimental group）. Primary-myoblasts were injected into 18 post-infraction rats （control group） and 12 non-infarction rats （sham group）. Expression of p16INK4a and PCNA pro- tein in myocardiums were separately detected immunocytochemically 1, 2 and 4 weeks after the inuection. The level of hIGF-1 and rIGF-1 protein in serum and myocardium were detected by en- zyme-linked immunosorbent assay （ELISA）. Compared with the sham group, the percentage of p^16INK4a and PCNA positive cells reached a peak after 1 week in the control group and the experimental group （P〈0.01）. Moreover, the percentage of p16^INK4a-positive cells in the experimental group was lower than in control group whereas the percentage of PCNA-positive cells was lower in the control group than in the experimental group （P〈0.01）. The percentage of p16^INK4a-positive cells in the experimental group and the percentage of PCNA-positive cells in the control group were close to that in the sham group from the 2nd week （P〉0.05）. ELISA analysis disclosed that the myocardium level of rIGF-1 protein increased gradually in the controls and especially in the experimental group （P〈0.01）. The serum level of rIGF-1 decreased significantly in post-infraction rats, but these conditions were improved in the experimental group （P〈0.01）. The hIGF-1 protein in serum and myocar- dium were detected from the 1st week to the 4th week in the experimental group. Statistical analysis revealed significant associations of myocardium level of hIGF-1 protein with expression of p^16INK4a and PCNA protein （r=–0.323, P〈0.05; r=0.647, P〈0.01）. It is concluded that genetically hIGF-1-myoblast provides a means for constant synthesis and release of hIGF-1. It could not only improve the expression of rIGF-1 and PCNA protein in myocardium, but also suppress the expression of p16^INK4a protein for 30 days in post-infraction rats. Myoblasts-mediated IGF-1 gene therapy may provide a new alternative for the clinical treatment of heart failure.
文摘Aberrant expression of the cell cycle kinase inhibitors p16,p21,and p27has been associated with poor prognosis in a variety of human malignancies.Litt le is known,however,about their clinical impact in vulvar carcinoma patients.Thus,we analyzed a larger series of v ulvar squamous cell carcinomas and compared the results with clinical outcome.A total of 224vulvar squamous cell carcinomas were im-munohistochemically investigated for expression of p16,p21,and p27using the biotin -strept avidin -peroxidase method and the OptiMax Plus automate d cell staining sys-tem.High p16(≥5%)positive nuclear immunostaining was found in 69(31%)cases,high p21(any staining)protein levels was detected in 95(42%)cases,and lowp27(≤50%positive nuclei)staining was seen in 170(76%)cases.High expression of p16was related to lower patient age and low expression of p53.High expression of p16indicated a better prognosis in t he multivariate analysis(RR =0.5,95%CI =0.2-1.0)and less risk of de-veloping lymph node metastasis(OR =0.3,95%CI =0.2-0.7).High level of p21was significantly associated with shorter survival in patients staged FIGO I and II(RR=3.4,95%CI =1.3-9.3).We found no significant correlation between the expression of p27and any of the clinicopathological variables.Our study indicates a prog-nostic relevance for p16and p21immu noreactivity.Low level of p16protein and high level of p21protein were as-sociated with a shorter disease -related survival.We did not find p27protein expression to be useful as a prognostic indicator in vulvar carcinoma patie nts.
