Relation between c-erbB1, c-erbB2, MAPK expression and resistance to tamoxifen in breast cancer cells in vitro.
- Author:
Qing-yuan ZHANG
1
;
Wen-hui ZHAO
;
Xin-mei KANG
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents, Hormonal; pharmacology; Blotting, Western; Breast Neoplasms; genetics; metabolism; pathology; Cell Line, Tumor; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; drug effects; Humans; Immunohistochemistry; Mitogen-Activated Protein Kinases; metabolism; Phosphorylation; drug effects; RNA, Messenger; biosynthesis; genetics; Receptor, Epidermal Growth Factor; biosynthesis; genetics; Receptor, ErbB-2; biosynthesis; genetics; Receptor, ErbB-3; biosynthesis; genetics; Receptor, ErbB-4; Reverse Transcriptase Polymerase Chain Reaction; Tamoxifen; pharmacology
- From: Chinese Journal of Oncology 2006;28(11):826-830
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the growth regulation pathway and the mechanism of acquired resistance to tamoxifen (TAM) in breast cancer cells.
METHODSTAM was used to induce wild-type MCF-7 human breast cancer cell line and establish a tamoxifen-resistant (TAM-R) cell line. RT-PCR, Western blot and immuocytochemical techniques were used to detect and compare mRNA and protein of c-erbB1, cerbB2, c-erbB3, c-erbB4 in wild-type MCF-7 and TAM-R MCF-7 cell lines.
RESULTSCompared with wild-type MCF-7 cells, the mRNA of c-erbB1 increased 6 times (P < 0.05) and the protein 3 times higher (P < 0.05), and the mRNA of c-erbB2 increased 3 times (P < 0.05) and the protein 1.5 times higher (P < 0.05) in TAM-R MCF-7 cells. However, comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. c-erbB4 could not be detected. Under basic conditions, phosphorylated c-erbB1/c-erbB2 and c-erbB1/c-erbB3 heterodimers but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased level of phosphorylated MAPK.
CONCLUSIONOur findings demonstrated that the development of TAM-resistance in MCF-7 cells is related with the autocrine release and action of an c-erbB1-specific ligand inducing preferential c-erbB1/c-erbB2 dimerization and downstream activation of the MAPK pathway.
