Department of Medicine, Indiana University School of Medicine, Walther Hall, 980 W Walnut Street, C230, Indianapolis, IN 46202, USA.
Breast Cancer Res Treat. 2010 Nov;124(2):327-35. doi: 10.1007/s10549-010-0733-2. Epub 2010 Jan 23.
Protein kinase C betaII (PKCβII) represents a novel potential target for anticancer therapies in breast cancer. In order to identify patient subgroups which might benefit from PKC-targeting therapies, we investigated the expression of PKCβII in human breast cancer cell lines and in a tissue microarray (TMA). We first screened breast cancer cell line representatives of breast cancer subtypes for PKCβII expression at the mRNA and at the protein levels. We analyzed a TMA comprising of tumors from 438 patients with a median followup of 15.4 years for PKCβII expression by immunohistochemistry along with other prognostic factors in breast cancer. Among a panel of human breast cancer cell lines, only MDA-MB-436, a triple negative basal cell line, showed overexpression for PKCβII both at the mRNA and at the protein levels. In breast cancer patients, cytoplasmic expression of PKCβII correlated positively with human epidermal growth factor receptor-2 (HER-2; P = 0.01) and Ki-67 (P = 0.016), while nuclear PKCβII correlated positively with estrogen receptor (ER; P = 0.016). The positive correlation of CK5/6 with cytoplasmic PKCβII (P = 0.033) lost statistical significance after adjusting for multiple comparisons (P = 0.198). Cytoplasmic PKCβII did not correlate with cyclooxygenase (COX-2; P = 0.925) and vascular endothelial growth factor (P = 1). There was no significant association between PKCβII staining and overall survival. Cytoplasmic PKCβII correlates with HER-2 and Ki-67, while nuclear PKCβII correlates with ER in breast cancer. Our study suggests the necessity for assessing the subcellular localization of PKCβII in breast cancer subtypes when evaluating the possible effectiveness of PKCβII-targeting agents.
蛋白激酶 CβII（PKCβII）是乳腺癌中一种新的潜在抗癌治疗靶点。为了确定可能受益于 PKC 靶向治疗的患者亚组，我们研究了 PKCβII 在人乳腺癌细胞系和组织微阵列（TMA）中的表达。我们首先筛选了代表乳腺癌亚型的乳腺癌细胞系，以确定 PKCβII 在 mRNA 和蛋白水平上的表达。我们分析了一个包含 438 例患者的 TMA，这些患者的中位随访时间为 15.4 年，通过免疫组织化学分析了 PKCβII 的表达以及乳腺癌中的其他预后因素。在一组人乳腺癌细胞系中，只有 MDA-MB-436，一种三阴性基底细胞系，在 mRNA 和蛋白水平上均显示 PKCβII 的过度表达。在乳腺癌患者中，PKCβII 的细胞质表达与人类表皮生长因子受体-2（HER-2；P = 0.01）和 Ki-67（P = 0.016）呈正相关，而核 PKCβII 与雌激素受体（ER；P = 0.016）呈正相关。在调整了多次比较后（P = 0.198），CK5/6 与细胞质 PKCβII 的正相关性（P = 0.033）失去了统计学意义。细胞质 PKCβII 与环氧化酶（COX-2；P = 0.925）和血管内皮生长因子（P = 1）无显著相关性。PKCβII 染色与总生存期无显著相关性。细胞质 PKCβII 与 HER-2 和 Ki-67 相关，而核 PKCβII 与 ER 相关。本研究提示，在评估 PKCβII 靶向药物的可能疗效时，有必要评估乳腺癌亚型中 PKCβII 的亚细胞定位。
