Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China; Department of Obstetrics and Gynaecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
Biochem Biophys Res Commun. 2013 Nov 1;440(4):652-7. doi: 10.1016/j.bbrc.2013.09.121. Epub 2013 Oct 4.
Breast cancer is the most common hormone-dependent malignancy in women. Homeobox (HOX) transcription factors regulate many cellular functions, including cell migration, proliferation and differentiation. The aberrant expression of HOX genes has been reported to be associated with human reproductive cancers. Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER-beta, are known to play critical roles in the regulation of breast cancer cell growth. However, an understanding of the potential relationship between HOXA7 and ER in breast cancer cells is limited. In this study, our results demonstrate that knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and ERα expression. In addition, HOXA7 knockdown attenuated E2-induced cell proliferation as well as progesterone receptor (PR) expression. The stimulatory effects of E2 on cell proliferation and PR expression were abolished by co-treatment with ICI 182780, a selective ERα antagonist. In contrast, overexpression of HOXA7 significantly stimulated cell proliferation and ERα expression. Moreover, E2-induced cell proliferation, as well as PR expression, was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic role for HOXA7 in modulating breast cancer cell proliferation via regulation of ERα expression. This finding contributes to our understanding of the role HOXA7 plays in regulating the proliferation of ER-positive cancer cells.
乳腺癌是女性最常见的激素依赖性恶性肿瘤。同源盒（HOX）转录因子调节许多细胞功能，包括细胞迁移、增殖和分化。HOX 基因的异常表达与人类生殖系统癌症有关。雌二醇（E2）及其核受体，雌激素受体（ER）-α和 ER-β，已知在调节乳腺癌细胞生长中起关键作用。然而，HOXA7 与 ER 在乳腺癌细胞中的潜在关系的理解是有限的。在这项研究中，我们的结果表明，在 MCF7 细胞中敲低 HOXA7 显著降低了细胞增殖和 ERα 表达。此外，HOXA7 敲低减弱了 E2 诱导的细胞增殖以及孕激素受体（PR）表达。E2 对细胞增殖和 PR 表达的刺激作用被选择性 ERα 拮抗剂 ICI 182780 的共同处理所消除。相比之下，HOXA7 的过表达显著刺激了细胞增殖和 ERα 表达。此外，E2 诱导的细胞增殖以及 PR 表达，通过 HOXA7 的过表达而增强。HOXA7 的敲低或过表达均不影响 ER-β 水平。我们的结果表明，HOXA7 通过调节 ERα 表达在调节乳腺癌细胞增殖中具有新的机制作用。这一发现有助于我们理解 HOXA7 在调节 ER 阳性癌细胞增殖中的作用。
