Department of Pathology, University of Alabama at Birmingham, Kaul 640B, 1530 Third Avenue South, Birmingham, AL 35294, USA.
Breast Cancer Res Treat. 2010 Aug;123(1):59-71. doi: 10.1007/s10549-009-0617-5. Epub 2009 Nov 10.
Gli1 is a transcription factor and oncogene with documented roles in the progression of several cancer types, including cancers of the skin and pancreas. The contribution of Gli1 to the progression of breast cancer is less established. In order to investigate the functional impact of Gli1 in breast cancer, expression of Gli1 and its contribution to cell growth was assessed in breast cancer cell lines. These in vitro results were compared to expression of Gli1, determined by immunohistochemistry, in 171 breast cancers. In these cancers, the association of Gli1 with expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR), ErbB2, p53, the rate of proliferation, and clinicopathologic parameters and outcome was assessed. Expression of Gli1 and ERalpha mRNA was strongly correlated in ERalpha-positive cell lines (r = 0.999). Treatment with estrogen increased expression of Gli1 in 2 of 3 ERalpha-positive cell lines; this increase was prevented by treatment with the ERalpha-specific antagonist MPP. Silencing of Gli1 by shRNA markedly reduced the survival of two ERalpha-negative cell lines, but caused only a modest reduction in ERalpha-positive cell lines. In breast cancer tissues, cancers with nuclear localization of Gli1 had a higher ERalpha (P=0.027) and lower p53 expression (P=0.017) than those without nuclear localization of Gli1. However, nuclear localization of Gli1 was predictive of a poorer cancer-specific survival in ERalpha-negative, including triple negative, cancers (P = 0.005), but not ERalpha-positive cancers. In conclusion, we demonstrate a positive association between expression of Gli1 and ERalpha; however, our data indicate a greater functional effect of Gli1 in ERalpha-negative cancers.
Gli1 是一种转录因子和癌基因，其在多种癌症类型的进展中具有明确的作用，包括皮肤癌和胰腺癌。Gli1 对乳腺癌进展的贡献尚未确定。为了研究 Gli1 在乳腺癌中的功能影响，评估了 Gli1 在乳腺癌细胞系中的表达及其对细胞生长的贡献。将这些体外结果与 171 例乳腺癌中通过免疫组织化学测定的 Gli1 表达进行了比较。在这些癌症中，评估了 Gli1 与雌激素受体 alpha (ERalpha) 和孕激素受体 (PR)、ErbB2、p53、增殖率以及临床病理参数和结局的关联。在 ERalpha 阳性细胞系中，Gli1 和 ERalpha mRNA 的表达呈强相关性(r = 0.999)。在 3 种 ERalpha 阳性细胞系中的 2 种中，用雌激素处理会增加 Gli1 的表达；用 ERalpha 特异性拮抗剂 MPP 处理可防止这种增加。用 shRNA 沉默 Gli1 可显著降低 2 种 ERalpha 阴性细胞系的存活率，但对 ERalpha 阳性细胞系的影响较小。在乳腺癌组织中，具有核定位的 Gli1 的癌症比没有核定位的 Gli1 的癌症具有更高的 ERalpha(P=0.027)和更低的 p53 表达(P=0.017)。然而，核定位的 Gli1 可预测 ERalpha 阴性(包括三阴性)癌症的癌症特异性生存率较差(P = 0.005)，但对 ERalpha 阳性癌症则不然。总之，我们证明了 Gli1 表达与 ERalpha 之间存在正相关；然而，我们的数据表明，Gli1 在 ERalpha 阴性癌症中的功能影响更大。
