Induction of estrogen receptor α-36 expression by bone morphogenetic protein 2 in breast cancer cell lines

Abstract

Abstract. 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.

Genetic variation in bone morphogenetic proteins and breast cancer risk in hispanic and non‐hispanic white women: The breast cancer health disparities study

“…However, rare haplotypes of these genes were associated with breast cancer risk, primarily among women with intermediate and high Native American ancestry. Given associations observed between menopausal status and ER/PR tumor status, we believe that our data support the findings by Takahashi and Wang that showed the importance of BMP receptors and estradiol 9, 25 . Many of our associations by ER and PR status were observed for type 1 receptors ( ACVR1 and ACVRL1 ).…”

Pubertal high fat diet: effects on mammary cancer development

“…BMPs are recognized as key regulators during the control of cell fate and cancer development [58], and BMP signaling can downregulate levels of mitotic checkpoint components in human breast cancer cells [59]. Bmp7 has also been implicated in increasing the metastatic potential of 4 T1 mouse mammary tumor cells [60].…”

Circulating oestrogen receptor mutations and splice variants in advanced prostate cancer

“…Previously described primer pairs that could specifically amplify the region of interest were identified for all ESR1 mutations, as well as the ERα‐66 and ERα‐36 splice variants . Primer pairs for the ERβ splice variants ERβ1, ERβ2, ERβ4 and ERβ5 were designed for the present study (Table S1).…”