[The Methylation of p16 Gene Promoter in Carcinogenesis and Development of Breast Cancer].

OBJECTIVE: To investigate the protein expression of the p16 gene and the methylation of its promoter in breast cancer, and to analyze the correlation between the p16 DNA methylation and the clinicopathological features. METHODS: Immuno-histochemistry technique (SP method) and methylation-specific-PCR (MSP) were used to detect p16 protein expression and the methylation of the p16 promoter in 47 breast cancer samples as well as in 20 hyperplasia samples of mammary glands. Results The p16 protein expression in breast cancer samples significantly lower when compared with those of hyperplasia samples (48. 9% vs. 70. 0%) and p16 methylation was more frequent in breast-tumor tissues when compared with those of hyperplasia samples (38. 3% vs. 20. 0%), but the statistical significance wasn't found (P> 0. 05). Down-regulation of p16 protein was negatively correlation with p16 gene hypermethylation (r= -0. 33, P =0. 02). Meanwhile, p16 methylation in breast cancer tissues correlated with histological type, lymph node metastasis, but not correlated with the age, tumor diameter, TNM stage, expression of estrogen receptor (ER) and progesterone receptor (PR) gene status. CONCLUSION: The downregulation of p16 protein induced by promoter methylation of p16 gene may not contribute to early cancinogenesis, but may contribute to progression of breast cancer.

[Alteration of apoptosis and Akt/mTOR signal pathway in hippocampal neurons of rat with post-traumatic stress].

OBJECTIVE: To observe the changes of apoptosis and protein kinase B/the mammalian target of Rapamycin (Akt/mTOR) signal pathway in hippocampal neurons of rat with post-straumatic stress disorder (PTSD), and to investigate the mechanism of PTSD. METHODS: Sixty male adult SD rats were divided into control group (n = 10) and PTSD (n = 50) model group. The PTSD animal model was established by giving the rats single-prolonged stress followed a single inescapable electric foot shock (SPS & S). The neuronal apoptosis of hiappocampus of PTSD rats at 1 d, 4 d, 7 d, 14 d and 28 d after model established was detected by flow cytometry (FCM). The expressions of phosphatase and tensin homology deleted on chromosome Ten (PTEN), phosphorylation of ARt and mTOR (p-Akt and p-mTOR) protein were detected by Western blotting. RESULTS: The apoptotic cell rate in PTSD 1 d, 4 d, 7 d and 14 d rats were higher than that in control rats (P < 0.05). The PTEN expression level was higher since PTSD 1 d than that in control group, and peaked in PTSD 4 d (P < 0.05). The p-Akt expression level was lower in PTSD 1 d than that in control group, and then increased in various time points after PTSD, but it was still lower in PTSD 28 d (P < 0.05). The p-mTOR expression level was lower than that in control group since PTSD 4 d, and then increased in various time points after PTSD 4 d, but it was still lower in PTSD 28 d (P < 0.05). CONCLUSION: The Akt/mTOR signal pathway was actived in hippocampal neurons of PTSD rats, and which was involved in neuronal apoptosis regulation.