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 / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 594-597, 2004.
Article
in Chinese
| WPRIM
| ID: wpr-254278
ABSTRACT
<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Lipofectin-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.</p><p><b>RESULTS</b>Eighteen 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.</p><p><b>CONCLUSION</b>Overexpression 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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Radiation Tolerance
/
Breast Neoplasms
/
Transfection
/
Signal Transduction
/
Gene Expression Regulation, Neoplastic
/
Cesium Radioisotopes
/
Morpholines
/
Tumor Suppressor Protein p53
Limits:
Female
/
Humans
Language:
Chinese
Journal:
Chinese Journal of Oncology
Year:
2004
Type:
Article
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