Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China,
J Mol Histol. 2014 Apr;45(2):169-80. doi: 10.1007/s10735-013-9546-z. Epub 2013 Oct 23.
Ski-interacting protein (SKIP) is a nuclear hormone receptor-interacting cofactor, interactions with the proto-oncogene Ski, appears to modulate a number of signalling pathways involved in control of cell proliferation and differentiation, and may play a critical role in oncogenesis. In the present study, to investigate the potential roles of SKIP in breast cancer, expression patterns, interaction and the correlation with clinical/prognostic factors of SKIP and Ki-67 were examined among patients with breast cancer. Immunohistochemistry and Western blot analysis were performed for SKIP in 85 breast carcinoma samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance. We found that SKIP was over expressed in breast carcinoma as compared with the adjacent normal tissues. High expression of SKIP was positively associated with histological grade (P = 0.01) and Ki-67 (P = 0.004). Univariate analysis showed that SKIP expression was associated with a poor prognosis (P = 0.006). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of SKIP was up-regulated, whereas p27 was down-regulated. In addition, we employed small interfering RNA (siRNA) technique to knock down SKIP expression and observed it effects on MDA-MB-231 cells growth. SKIP depletion by siRNA inhibited cell proliferation, blocked S phase and decreased cyclin A and cyclin B levels. On the basis of these results, we suggested that SKIP overexpression was involved in the pathogenesis of breast cancer, which might serve as a future target for breast cancer.
Ski 相互作用蛋白（SKIP）是核激素受体相互作用的共因子，与原癌基因 Ski 相互作用，似乎调节了许多参与控制细胞增殖和分化的信号通路，并且在肿瘤发生中可能发挥关键作用。在本研究中，为了研究 SKIP 在乳腺癌中的潜在作用，检测了 SKIP 在乳腺癌患者中的表达模式、相互作用及其与临床/预后因素的相关性。对 85 例乳腺癌样本进行了 SKIP 的免疫组织化学和 Western blot 分析。将数据与临床病理特征相关联。还进行了单变量和多变量生存分析以确定其预后意义。我们发现 SKIP 在乳腺癌中过表达，与相邻的正常组织相比。SKIP 的高表达与组织学分级（P = 0.01）和 Ki-67（P = 0.004）呈正相关。单变量分析表明 SKIP 表达与预后不良相关（P = 0.006）。而在体外，当乳腺癌细胞系从血清饥饿中释放时，SKIP 的表达上调，而 p27 的表达下调。此外，我们采用小干扰 RNA（siRNA）技术敲低 SKIP 表达，观察其对 MDA-MB-231 细胞生长的影响。siRNA 敲低 SKIP 表达抑制细胞增殖，阻断 S 期并降低细胞周期蛋白 A 和细胞周期蛋白 B 的水平。基于这些结果，我们认为 SKIP 的过表达参与了乳腺癌的发病机制，可能成为乳腺癌的未来治疗靶点。
