Autocrine human growth hormone expression leads to resistance of MCF-7 cells to tamoxifen.
Tamoxifen is the most common antiestrogen used in the treatment of estrogen-positive breast cancer but its adverse effects and also resistance to this drug are serious challenges in the treatment of breast cancer. Characterization of mechanisms responsible for these adverse effects can lead to design of more efficient therapeutic strategies for the treatment of breast cancer. Here, we used a cellular model to evaluate the effects of autocrine expression of human growth hormone on responses of cells to tamoxifen. Our results imply for the first time that autocrine expression of growth hormone in human breast adenocarcinoma cell line, MCF-7, results in increase in cell proliferative capacity of cells even in the presence of tamoxifen. This effect may be due to up-regulation of G-coupled estrogen receptor, GPR30, which is activated by tamoxifen.
Mojarrad
Majid
M
Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.
Momeny
Majid
M
Mansuri
Fatemeh
F
Abdolazimi
Yassan
Y
Tabrizi
Mina Hajifaraj
MH
Ghaffari
Seyed Hamidollah
SH
Tavangar
Seyed Mohammad
SM
Modarressi
Mohammad Hussein
MH
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019898:Autocrine Communication / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019382:Human Growth Hormone / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
D013629:Tamoxifen; D019382:Human Growth Hormone