Induction of estrogen receptor α-36 expression by bone morphogenetic             protein 2 in breast cancer cell lines.
The expression of estrogen receptor-α (ERα) is one of the most important             diagnostic and prognostic factors of breast cancer. Recently, ERα-36 has been             identified as a novel variant of ER-α. ERα-36 lacks intrinsic transcription activity             and mainly mediates non-genomic estrogen signaling. Bone morphogenetic proteins             (BMPs) are recognized as key factors during the control of cell fate and cancer             development. However, the correlation between BMP and the ER signaling pathway             remains unclear. In this study, we show that BMP2, a member of the BMP family,             is a novel inducer of ERα-36 expression in breast cancer cells. As shown by western             blot assays, the upregulation of ERα-36 by BMP2 was significant. In MDA-MB-231             cells which are ERα-66-negative, BMP2 was able to induce the expression of ERα-36             in a dose-dependent manner, and the RNA interference assay indicated a correlation             between BMP2 and ERα-36 expression. BMP2 inhibited the growth of MCF-7 and MDA-MB-231             cells; however, the inhibitory effect was antagonized by tamoxifen, suggesting             that the ER signal was involved. The growth of MDA-MB‑231 cells was stimulated             by 17-β-estradiol (E2) after BMP2 induction, even though the cells were previously             insensitive to E2. These results suggest that BMP2 induces ERα-36 expression and             alters tumor resistance to endocrine therapy by changing the expression profile             of ERs.
Department of Biotechnology, Institute of Life Science and Biological Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
Dingding
D
Wang
Peide
P
Huang
Baowei
B
Zhu
Li
L
Sun
Qing
Q
Huang
Ju
J
Wang
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D055396:Bone Morphogenetic Protein 2; D047628:Estrogen Receptor alpha; D004967:Estrogens; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D013629:Tamoxifen; D004958:Estradiol; C498211:BMPR1A protein, human; C498214:BMPR1B protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I