Department of Gynecologic Oncology, The First Clinical Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Int J Oncol. 2013 Dec;43(6):1925-34. doi: 10.3892/ijo.2013.2124. Epub 2013 Oct 3.
Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (p<0.05) and in tissue with a T4 tumor stage (p<0.01). Thus, BCCIP protein was chiefly reduced in ovarian cancer and RCC tissue samples (p<0.05). BCCIP gene expression was downregulated in human ovarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.
人 BCCIP 蛋白与 BRCA2 和 CDKN1A（Cip1，p21）相互作用，参与多种细胞过程，包括细胞周期调控、DNA 重组和修复、端粒维持、胚胎发育和基因组稳定性。BCCIP 基因表达是肿瘤抑制中的重要 BRCA2 共因子，已在一些原发性癌症中得到鉴定。因此，我们研究了 BCCIP 表达在大量临床诊断的原发性卵巢癌、肾细胞癌（RCC）和结直肠癌（CRC）组织中的作用。使用临床诊断的冷冻原发性癌症组织，采用定量 PCR（qPCR）、western blot 分析（WB）和免疫组织化学染色（IHC）方法检测和测量基因表达。卵巢癌、RCC 和 CRC 组织中 BCCIP 基因表达降低分别发生在 74%、89%和 75%的组织样本中。对 54 例卵巢癌、50 例 RCC 和 44 例 CRC 样本的 mRNA 表达 qPCR 分析显示，组织样本中分别有 56%、70%和 46%的组织样本中 BCCIP 下调超过 2 倍。尽管三种不同的肿瘤组织中 BCCIP 表达降低，但 BCCIP 表达与每种癌症的临床病理特征之间的关系是不同的。与正常组织相比，BCCIP 在浆液性、内异症和黏液性癌中的表达明显下调。BCCIP 表达下调与透明细胞 RCC（ccRCC）和 Fuhrman 肿瘤分级密切相关，但仅在男性 CRC 组织（p<0.05）和 T4 期肿瘤组织（p<0.01）中发现 CRC 及其匹配正常组织之间的 BCCIP 表达存在显著差异。因此，BCCIP 蛋白主要在卵巢癌和 RCC 组织样本中减少（p<0.05）。BCCIP 基因在人卵巢癌、RCC 和 CRC 组织中表达下调，提示该基因在这些癌症的发病机制中起作用。
