[Relation between c-erbB1, c-erbB2, MAPK expression and resistance to tamoxifen in breast cancer cells in vitro].
OBJECTIVE
To study the growth regulation pathway and the mechanism of acquired resistance to tamoxifen (TAM) in breast cancer cells.


METHODS
TAM 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.


RESULTS
Compared 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.


CONCLUSIONS
Our 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.
Zhang
Qing-yuan
QY
The Third Department of Internal Medicine, Tumor Hospital, Harbin Medical University, Harbin 150040, China. zhma19650210@163.com
Zhao
Wen-hui
WH
Kang
Xin-mei
XM
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000096:biosynthesis / Q000235:genetics; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*
D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D013629:Tamoxifen; C587689:ERBB4 protein, human