Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
J Transl Med. 2012 Sep 19;10 Suppl 1(Suppl 1):S2. doi: 10.1186/1479-5876-10-s1-s2.
Estrogen plays an important role in the development of estrogen-dependent breast carcinoma. Recently, several studies demonstrated a possible involvement of several micro RNAs (miRNAs) in the development of resistance to endocrine therapy in breast cancer patients, but the correlation between estrogen actions and miRNA expression in breast carcinoma still remains largely unknown. Therefore, in this study, we examined the in vitro effects of estrogen upon miRNA expression profiles in breast carcinoma.
We first screened the miRNA expression profiles induced by 17β-Estradiol (E2) using RT2 miRNA PCR Array in the ER-positive breast carcinoma cell line MCF-7. We identified miR-7 as the important miRNA associated with estrogen actions in these cells and further examined the changes of estrogen-dependent EGFR expression by miR-7 in ER-positive or -negative breast carcinoma cell lines including MCF-7. We also evaluated the correlation between miR-7 and EGFR expression in breast carcinoma cells derived from 21 patients using laser capture microdissection combined with quantitative reverse transcriptase-PCR.
Seventeen miRNAs were significantly induced by E2 treatment in the MCF-7 cell line. Among 17 miRNAs induced by estradiol treatment, only miR-7 expression was significantly decreased by subsequent ICI treatment. The expression of miR-7 was up-regulated 2.94-fold by E2 treatment. miR-7 was reported to suppress epidermal growth factor receptor (EGFR) expression in several human malignancies. Transfection of miR-7 significantly suppressed EGFR mRNA levels in MCF-7 cells. Depletion of E2 from cell culture media also increased the expression level of EGFR mRNA in MCF-7 and T-47D cells but not in ER-negative, MDA-MB-231 and SK-BR-3 cells. We also evaluated the status of miR-7 in breast carcinoma tissues, but the correlation between the status of miR-7 and EGFR in carcinoma cells isolated by laser capture microscopy was not detected.
These results suggest that miR-7 may play a role in the development of resistance to endocrine therapy in breast cancer patients through regulating EGFR expression of carcinoma cells.
雌激素在雌激素依赖性乳腺癌的发展中起着重要作用。最近，几项研究表明，几种 microRNAs（miRNAs）可能参与了乳腺癌患者内分泌治疗耐药的发生，但雌激素作用与乳腺癌中 miRNA 表达之间的相关性仍知之甚少。因此，在本研究中，我们研究了雌激素对乳腺癌细胞中 miRNA 表达谱的体外影响。
我们首先使用 RT2 miRNA PCR 阵列筛选 17β-雌二醇（E2）诱导的 MCF-7 雌激素受体阳性乳腺癌细胞系中的 miRNA 表达谱。我们发现 miR-7 是与这些细胞中雌激素作用相关的重要 miRNA，并进一步研究了 miR-7 在包括 MCF-7 在内的雌激素受体阳性或阴性乳腺癌细胞系中对雌激素依赖性 EGFR 表达的变化。我们还使用激光捕获显微切割联合定量逆转录聚合酶链反应评估了 21 例乳腺癌患者的细胞中 miR-7 与 EGFR 表达之间的相关性。
E2 处理后 MCF-7 细胞系中有 17 种 miRNA 明显上调。在雌二醇处理诱导的 17 种 miRNA 中，只有 miR-7 的表达在后续 ICI 处理后显著降低。E2 处理使 miR-7 的表达上调了 2.94 倍。miR-7 被报道可在几种人类恶性肿瘤中抑制表皮生长因子受体（EGFR）的表达。miR-7 的转染显著抑制了 MCF-7 细胞中 EGFR mRNA 的水平。从细胞培养物中去除 E2 也增加了 MCF-7 和 T-47D 细胞中 EGFR mRNA 的表达水平，但在 ER 阴性、MDA-MB-231 和 SK-BR-3 细胞中没有增加。我们还评估了 miR-7 在乳腺癌组织中的状态，但未检测到激光捕获显微镜分离的癌组织中 miR-7 与 EGFR 状态之间的相关性。
这些结果表明，miR-7 可能通过调节癌细胞中的 EGFR 表达在乳腺癌患者内分泌治疗耐药的发生中起作用。
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