Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China.
Steroids. 2012 May;77(6):666-73. doi: 10.1016/j.steroids.2012.02.013. Epub 2012 Feb 27.
Estrogen receptor-alpha 36 (ER-α36) is a variant of ER-α that has been found to be expressed in conventional ER (ER-α66)-negative breast cancer cell lines and human breast cancer samples. In this study, we found that, using immunohistochemical study, ER-α36 expression was significantly higher in ER-negative tumors than in ER-positive tumors although the expression was not associated with other clinicopathological characteristics. We then constructed an ER-α36-specific microRNA hairpin vector and established stable ER-α36 knockdown cells, and found that the knockdown cells were more sensitive to paclitaxel; the c-Jun N-terminal kinase pathway appeared to be involved in the mechanism. Downregulation of ER-α36 also resulted in decreased migration and invasion. These changes were estrogen independent. Our findings indicated that target ER-α36 may be a strategy for treating ER-negative breast cancers.
雌激素受体-α 36（ER-α36）是 ER-α 的一种变体，已在常规 ER（ER-α66）阴性乳腺癌细胞系和人乳腺癌样本中发现其表达。在这项研究中，我们发现，通过免疫组织化学研究，尽管 ER-α36 的表达与其他临床病理特征无关，但在 ER 阴性肿瘤中的表达明显高于 ER 阳性肿瘤。然后，我们构建了一个 ER-α36 特异性 microRNA 发夹载体，并建立了稳定的 ER-α36 敲低细胞，发现敲低细胞对紫杉醇更敏感；c-Jun N-末端激酶途径似乎参与了该机制。ER-α36 的下调还导致迁移和侵袭减少。这些变化与雌激素无关。我们的研究结果表明，靶向 ER-α36 可能是治疗 ER 阴性乳腺癌的一种策略。
