Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, PR China.
Mol Med Rep. 2012 Feb;5(2):305-12. doi: 10.3892/mmr.2011.634. Epub 2011 Oct 18.
In the female population in Asia, systematic investigation concerning alterations in cancer-related genes in breast carcinoma is rare, and the correlation among oncogene or suppressor gene expression with tumor cell apoptosis, cell cycle regulation and tumor cell autophagy remains to be clarified. In this study, a tissue microarray consisting of 360 individual samples from three different breast tissues was generated. By comparing the expression of the tumor-suppressor genes (BRCA1, BECN1, CCND1, PTEN and UVRAG) in ductal breast cancer and normal breast tissues, respectively, we were able to assign changes in the expression of these mRNAs to specific stages and allocate them to define the roles in the multi‑step process of breast carcinogenesis. Tumor-suppressor genes, such as BRCA1 and BECN1, usually had lower signals in the carcinomatous tissues (10.2 and 6.6%) compared to the normal tissues (31 and 32.6%), while stronger positive dots (positive cells >30%) usually existed in the normal tissues. The patients in the oldest age group had the lowest expression rate. Only BECN1 and CCND1 expression showed a significant association with patient age (p=0.030 and p=0.003). A significant association was observed between BRCA1 and BECN1 expression and tumor size (p=0.028 and p=0.021). BECN1 gene expression was positively correlated with UVRAG and PTEN expression (p=0.006 and p=0.000). CCND1 was negatively correlated with PTEN, BECN1 and BRCA1 expression (p=0.011, p=0.000 and p=0.000). Abnormal expression of BRCA1, BECN1, CCND1, PTEN and UVRAG may play a role in human breast carcinogenesis through dysregulated mRNA expression. Overexpressed CCND1 may shorten the G1 phase of the cell cycle, suppress cell apoptosis and contribute to the formation of invasive ductal carcinoma (IDC).
在亚洲女性人群中，针对乳腺癌中与癌症相关基因改变的系统研究较为罕见，并且关于癌基因或抑癌基因表达与肿瘤细胞凋亡、细胞周期调控和肿瘤细胞自噬之间的相关性仍有待阐明。在本研究中，构建了一个包含 360 个来自三种不同乳腺组织的个体样本的组织微阵列。通过比较导管乳腺癌和正常乳腺组织中肿瘤抑制基因（BRCA1、BECN1、CCND1、PTEN 和 UVRAG）的表达情况，我们能够将这些 mRNA 的表达变化分配到特定的阶段，并将其分配到定义乳腺癌发生的多步骤过程中的作用。BRCA1 和 BECN1 等肿瘤抑制基因在癌组织（10.2%和 6.6%）中的信号通常低于正常组织（31%和 32.6%），而正常组织中通常存在更强的阳性斑点（阳性细胞>30%）。年龄最大的患者组表达率最低。只有 BECN1 和 CCND1 的表达与患者年龄呈显著相关（p=0.030 和 p=0.003）。BRCA1 和 BECN1 的表达与肿瘤大小之间存在显著相关性（p=0.028 和 p=0.021）。BECN1 基因的表达与 UVRAG 和 PTEN 的表达呈正相关（p=0.006 和 p=0.000）。CCND1 与 PTEN、BECN1 和 BRCA1 的表达呈负相关（p=0.011、p=0.000 和 p=0.000）。BRCA1、BECN1、CCND1、PTEN 和 UVRAG 的异常表达可能通过失调的 mRNA 表达在人类乳腺癌发生中发挥作用。过表达的 CCND1 可能缩短细胞周期的 G1 期，抑制细胞凋亡，并有助于侵袭性导管癌（IDC）的形成。
