AIM: To describe the correlation between innunostaining patterns of p16 and CDK4 and prognosis in colorectal carcinoma.METHODS: Paraffin sections of 74 cases of colorectal carcinoma were analysed immunohistochemically...AIM: To describe the correlation between innunostaining patterns of p16 and CDK4 and prognosis in colorectal carcinoma.METHODS: Paraffin sections of 74 cases of colorectal carcinoma were analysed immunohistochemically for expression of p16 and CDK4 proteins.RESULTS: Most carcinomas showed stronger p16 and CDK4immunostaining in the cytoplasm than the adenomas or the adjacent normal mucosa. Strong immunostaining of p16 was a predictor for better prognosis whereas strong cytoplasmic immunostaining of CDK4 was a predictor for poor prognosis.Both p16 and CDK4 immunostainings were correlated with histological grade or Dukes' stage.CONCLUSION: These results support the experimental evidence that interaction of expression of p16 and CDK4may play an important role in the Rb/p16 pathway, and the expression paterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.展开更多
To study the role of cyclinD 1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line （2BS） induced by silica. Methods Recombination vectors with sense and antisense pXJ41-cyclinD1 and...To study the role of cyclinD 1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line （2BS） induced by silica. Methods Recombination vectors with sense and antisense pXJ41-cyclinD1 and pXJ41-CDK4 were constructed, and then transfected into the malignant transformed cells induced by silica, respectively. At the same time, pXJ41-neo was used as the control. Results During the progress of the malignant transformation of 2BS cells induced by silica, cyclinD 1 and CDK4 were overexpressed. Antisense RNA suppressed cyclinD 1 and CDK4 gene expression in the antisense pXJ41-cyclinD1 and pXJ41-CDK4 transfected cells. Antisense RNA led to cell cycle arrest, resulting in lengthened G1 phase （the percentages of cells in the G1 phase changed from 45.1% to 52.7% and 58.0% for cyclinD1 and CDK4 transfected cells, respectively）, and eventually attenuated the increase of the proliferation of malignant transformed cells induced by silica. Compared with malignant transformed cells induced by silica, cells transfected with antisense pXJ41-cyclinD1 and pXJ41-CDK4 showed obviously reduced growth rates. On the 8th day, the suppression rates were 58.69 and 77.43% （the growth rate of malignant transformed cells induced by silica was 100%）, doubling time changed from 21.0 h to 31.4 h and 21.0 h to 42.7 h, respectively, the growth capacities on soft agar of cells transfected by antisense pXJ41-cyclinD1 and pXJ41-CDK4 decreased obviously. Conclusion CyclinD 1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.展开更多
Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell p...Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.展开更多
文摘AIM: To describe the correlation between innunostaining patterns of p16 and CDK4 and prognosis in colorectal carcinoma.METHODS: Paraffin sections of 74 cases of colorectal carcinoma were analysed immunohistochemically for expression of p16 and CDK4 proteins.RESULTS: Most carcinomas showed stronger p16 and CDK4immunostaining in the cytoplasm than the adenomas or the adjacent normal mucosa. Strong immunostaining of p16 was a predictor for better prognosis whereas strong cytoplasmic immunostaining of CDK4 was a predictor for poor prognosis.Both p16 and CDK4 immunostainings were correlated with histological grade or Dukes' stage.CONCLUSION: These results support the experimental evidence that interaction of expression of p16 and CDK4may play an important role in the Rb/p16 pathway, and the expression paterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.
基金This work was supported by grants from National Natural Science Foundation of China (30028019) and 973 National Key BasicResearch and Development Program (2002 CB 512906).
文摘To study the role of cyclinD 1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line （2BS） induced by silica. Methods Recombination vectors with sense and antisense pXJ41-cyclinD1 and pXJ41-CDK4 were constructed, and then transfected into the malignant transformed cells induced by silica, respectively. At the same time, pXJ41-neo was used as the control. Results During the progress of the malignant transformation of 2BS cells induced by silica, cyclinD 1 and CDK4 were overexpressed. Antisense RNA suppressed cyclinD 1 and CDK4 gene expression in the antisense pXJ41-cyclinD1 and pXJ41-CDK4 transfected cells. Antisense RNA led to cell cycle arrest, resulting in lengthened G1 phase （the percentages of cells in the G1 phase changed from 45.1% to 52.7% and 58.0% for cyclinD1 and CDK4 transfected cells, respectively）, and eventually attenuated the increase of the proliferation of malignant transformed cells induced by silica. Compared with malignant transformed cells induced by silica, cells transfected with antisense pXJ41-cyclinD1 and pXJ41-CDK4 showed obviously reduced growth rates. On the 8th day, the suppression rates were 58.69 and 77.43% （the growth rate of malignant transformed cells induced by silica was 100%）, doubling time changed from 21.0 h to 31.4 h and 21.0 h to 42.7 h, respectively, the growth capacities on soft agar of cells transfected by antisense pXJ41-cyclinD1 and pXJ41-CDK4 decreased obviously. Conclusion CyclinD 1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.
基金National Nature Science Foundation for Distinguished Young Scholar of China (No.39525022)National Basic Research Program(No.2004CB518703) National Nature Science Foundation of China (No.30570085).
文摘Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
