Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-ther...Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.展开更多
Gene mutation, rearrangement and amplification are frequently observed in mammary tumors. It is interesting to study if these genetic alterations are involved in DMBA-induced mammary tumors in 172￣(Arg-Leu) mutant p...Gene mutation, rearrangement and amplification are frequently observed in mammary tumors. It is interesting to study if these genetic alterations are involved in DMBA-induced mammary tumors in 172￣(Arg-Leu) mutant p￣(53) transgenic mice. The results of this study suggest that rearrangement of PCNA and H-ras contributed to the production of mammary tumors. No apparent gene amplification, however, was observed in these mammary tumors though several fold higher overexpression of cyclin D1 vs. normal was deteeted. The higher the expression level of 172￣(Arg-Leu) mutant p￣(53) in mammary gland of transgenic mice, the later the mammary tumor appeared in these mice. The 172￣(Arg-Leu) mutant p￣(53) in these mammary tumors behaved similarly to in vitro system.展开更多
Objective： The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer （TNBC）, and determine that whether p53 gene could be a new effective therapeutic target. Methods：...Objective： The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer （TNBC）, and determine that whether p53 gene could be a new effective therapeutic target. Methods： We identified studies with quantitative data on the relation of p53 gene and TNBC through searching 12 databases online （Oct. 1999-Oct. 2012） and reviewing the references, which were written in English or Chinese. Summary estimates of odds ratio （OR） was calculated using the fixed-effects model or the random-effects model as appropriate. Results： We identified 12 eligible stud- ies with 1532 cases of TNBC patients and 6329 controls of non-TNBC patients. The test for homogeneity resulted in X^2 = 200.16 （P 〈 0.05）, it showed significant heterogeneity so that a random effect model was applied. Our results showed that the expression of p53 gene could be much stronger in TNBC group than that in non-TNBC group [OR = 2.10, 95% confidence interval （CI） = 1.21-3.65]. In ethnicity-subgroup analysis, we found that in Caucasian group, the expression of p53 gene were stronger in TNBC group （OR = 2.60, 95% CI = 1.21-5.57）, but there was no statistical significance in Asian group （OR = 1.69, 95% CI = 0.83-3.45）. Conclusion： P53 gene could be an effective predictor and a good therapeutic target for TNBC patients in the future, especially in Caucasian. Further researches focusing on p53 gene would gain a breakthrough in the treatment of TNBC.展开更多
文摘Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.
文摘Gene mutation, rearrangement and amplification are frequently observed in mammary tumors. It is interesting to study if these genetic alterations are involved in DMBA-induced mammary tumors in 172￣(Arg-Leu) mutant p￣(53) transgenic mice. The results of this study suggest that rearrangement of PCNA and H-ras contributed to the production of mammary tumors. No apparent gene amplification, however, was observed in these mammary tumors though several fold higher overexpression of cyclin D1 vs. normal was deteeted. The higher the expression level of 172￣(Arg-Leu) mutant p￣(53) in mammary gland of transgenic mice, the later the mammary tumor appeared in these mice. The 172￣(Arg-Leu) mutant p￣(53) in these mammary tumors behaved similarly to in vitro system.
基金supported by a grant from the Key Project of National 12th Five-Years Research Program of China (No. 2012ZX-09303016-002)
文摘Objective： The aim of this study was to explore the relationship between p53 gene and triple-negative breast cancer （TNBC）, and determine that whether p53 gene could be a new effective therapeutic target. Methods： We identified studies with quantitative data on the relation of p53 gene and TNBC through searching 12 databases online （Oct. 1999-Oct. 2012） and reviewing the references, which were written in English or Chinese. Summary estimates of odds ratio （OR） was calculated using the fixed-effects model or the random-effects model as appropriate. Results： We identified 12 eligible stud- ies with 1532 cases of TNBC patients and 6329 controls of non-TNBC patients. The test for homogeneity resulted in X^2 = 200.16 （P 〈 0.05）, it showed significant heterogeneity so that a random effect model was applied. Our results showed that the expression of p53 gene could be much stronger in TNBC group than that in non-TNBC group [OR = 2.10, 95% confidence interval （CI） = 1.21-3.65]. In ethnicity-subgroup analysis, we found that in Caucasian group, the expression of p53 gene were stronger in TNBC group （OR = 2.60, 95% CI = 1.21-5.57）, but there was no statistical significance in Asian group （OR = 1.69, 95% CI = 0.83-3.45）. Conclusion： P53 gene could be an effective predictor and a good therapeutic target for TNBC patients in the future, especially in Caucasian. Further researches focusing on p53 gene would gain a breakthrough in the treatment of TNBC.
