[Effect of HSP90 function inhibited on the telomerase and P53 mutant in breast cancer cells].
OBJECTIVE
To investigate the effect of heat shock protein 90 (Hsp90) function inhibited on the telomerase activity and P53 expression in human breast cancer cells, in which a specific inhibitor geldanamycin (GA) was used to inhibit Hsp90 function.


METHODS
Human breast cancer cell line MDA-MB-435s was used for the study. Proliferation of MDA-MB-435s cells was measured with MTT assay. Cell cycle was analyzed by flow cytometry. The telomerase activity was measured by TRAP-ELISA assay. The protein expression of mutant P53 in cells was detected by Western blot.


RESULTS
GA inhibited the proliferation of MDA-MB-435s cells on a time- and dose-depending manner. After treated with GA, MDA-MB-435s cells arrested at G2/M phase. The telomerase activity of cells was decreasing, the expression level of mutant P53 protein in MDA-MB-435s cells was reduced obviously compared with that in control cells.


CONCLUSIONS
The telomerase activation and mutant P53 expression in MDA-MB-435s cells are related to HSP90 function, of which the inhibition with GA can decrease the telomerase activity and the protein expression of mutant P53, and further repress the proliferation of MDA-MB-435s cells.
Li
Xia
X
Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.
Deng
Hua-Yu
HY
D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation; D019098:Telomerase / Q000378:metabolism*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D050505:Mutant Proteins; D016159:Tumor Suppressor Protein p53; D019098:Telomerase; C001277:geldanamycin