Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, Japan.
Endocr Relat Cancer. 2012 Nov 6;19(6):741-50. doi: 10.1530/ERC-12-0017. Print 2012 Dec.
Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associated with the status of androgen receptor. KLF5 immunoreactivity was also significantly associated with increased risk of recurrence and worse clinical outcome in breast cancer patients by univariate analyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients. We then examined possible regulation of KLF5 by androgen using MCF-7 breast carcinoma cells. KLF5 mRNA was induced by biologically active androgen 5α-dihydrotestosterone in a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfection experiments demonstrated that proliferation activity of MCF-7 cells was significantly associated with the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive gene in human breast carcinomas and play important roles in the progression of breast carcinomas. KLF5 immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.
肠型 Kruppel 样因子 5（KLF5）或 Kruppel 样因子 5（KLF5）是一种含锌指的转录因子，参与包括细胞增殖和分化在内的重要生物学过程。然而，KLF5 蛋白在乳腺癌中的临床意义在很大程度上仍然未知。因此，在这项研究中，我们在 113 例人类乳腺癌病例中免疫定位了 KLF5。KLF5 免疫反应性经常在乳腺癌细胞的细胞核中检测到，KLF5 阳性癌细胞的中位数为 30%，并与雄激素受体的状态呈正相关。通过单因素分析，KLF5 免疫反应性与乳腺癌患者的复发风险增加和临床结局恶化显著相关，随后的多因素分析表明，KLF5 免疫反应性是患者无病和乳腺癌特异性生存的独立预后因素。然后，我们使用 MCF-7 乳腺癌细胞检查了雄激素对 KLF5 的可能调节作用。KLF5mRNA 在 MCF-7 细胞中以剂量和时间依赖性方式被生物活性雄激素 5α-二氢睾酮诱导。此外，转染实验的结果表明，MCF-7 细胞的增殖活性与 KLF5 的表达水平显著相关。这些发现表明，KLF5 是人类乳腺癌中的雄激素反应基因，在乳腺癌的进展中发挥重要作用。因此，KLF5 免疫反应性被认为是人类乳腺癌中的一种强有力的预后因素。
