The effect of HER2/neu overexpression on p53 gene expression, cell proliferation and sensitivity to gamma-irradiation via the PI3K/Akt pathway in breast cancer cell MCF7.
- Author:
Li ZHENG
1
;
Jia-qiang REN
;
Qi CHEN
;
Hui-ping ZHANG
;
Hong-guang ZHU
Author Information
- Publication Type:Journal Article
- MeSH: Breast Neoplasms; metabolism; pathology; Cell Line, Tumor; Cell Proliferation; drug effects; Cesium Radioisotopes; Chromones; pharmacology; Female; Gene Expression Regulation, Neoplastic; Genes, erbB-2; Humans; Morpholines; pharmacology; Phosphatidylinositol 3-Kinases; antagonists & inhibitors; metabolism; Proto-Oncogene Proteins c-akt; metabolism; Radiation Tolerance; Receptor, ErbB-2; biosynthesis; genetics; Signal Transduction; Transfection; Tumor Suppressor Protein p53; metabolism
- From: Chinese Journal of Oncology 2004;26(10):594-597
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of HER2/neu overexpression on the wild p53 gene expression, cell proliferation and sensitivity to gamma-irradiation via phosphatidylinositol 3-kinase (PI3K) pathway in human breast cancer cell MCF7.
METHODSLipofectin-mediated gene transfection method was used to transfer HER2/neu into MCF7 cells. Expression of HER2/neu, p53, Akt and p-Akt protein after PI3K pathway inhibitor LY294002 treatment was determined by Western blot. Cell proliferation and cell surviving fraction after gamma-irradiation treatment were assayed by MTT.
RESULTSEighteen of HER2/neu stably transfected MCF7 cell clones were established, one of them was HER2/neu overexpressing. HER2/neu overexpressing MCF7 cells showed higher p-Akt expression and lower p53 expression than those of parental MCF7 cells, which could be abrogated by LY294002. HER2/neu overexpressing MCF7 cells had higher proliferation rate and lower sensitivity to gamma-irradiation than those of parental MCF7 cells, which could be opposed by LY294002.
CONCLUSIONOverexpression of HER2/neu induces reduced expression of wild-type p53 protein, relatively high cell proliferation and low sensitivity to gamma-irradiation in breast cancer cell MCF7 by activating PI3K/Akt pathway, which may contribute to therapeutic resistance in some breast cancer patients with wild-type p53 gene status.
