Mao Xiao-Yun, Fan Chui-Feng, Wei Jing, Liu Cong, Zheng Hua-Chuan, Yao Fan, Jin Feng
Department of Breast Surgery, Department of Surgical Oncology, Research Unit of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, 110001, People's Republic of China.
Tumour Biol. 2011 Dec;32(6):1271-6. doi: 10.1007/s13277-011-0232-z. Epub 2011 Sep 10.
N-myc downstream-regulated gene-1 (NDRG1) has been identified as a protein involved in the differentiation of epithelial cells. As a newly metastasis suppressor gene, whether it contributes to carcinogenesis of breast cancer is still unknown. This study aimed to clarify the possible role of NDRG1 for breast cancer carcinogenesis, and further to investigate its clinicopathological significance in invasive breast cancer. We examined the expression of NDRG1 in normal epithelium of breast (n = 35), usual ductal hyperplasia (n = 22), atypical ductal hyperplasia (n = 33), atypical lobular hyperplasia (n = 8), ductal carcinoma in situ (n = 16), lobular carcinoma in situ (n = 6), invasive ductal carcinoma (n = 50), and invasive lobular carcinoma (n = 45) by immunohistochemistry and analyzed the correlation between NDRG expression and clinicopathological features of invasive breast cancer. Western blot analysis was carried out to investigate the expression of NDRG1 in 20 invasive ductal breast cancer and the paired non-tumor portion of the same case. NDRG1 expression in invasive breast cancer (70/95, 73.7%) was higher than that in noninvasive breast lesions (29/85, 34.1%; p < 0.05) which was higher than that in normal breast epithelium (5/35, 14.3%; p < 0.05). Statistical analysis revealed a significant correlation between NDRG1 expression with tumor stage in invasive breast cancer, and its expression in invasive ductal carcinoma is significantly higher than invasive lobular carcinoma (p < 0.05). It was not associated with age, menopausal status, tumor size, and lymph node metastasis. NDRG1 protein levels were significantly higher in invasive ductal breast cancer compared to the paired non-tumor portion of the same case by Western blot analysis (p < 0.05). Increased NDRG-1 expression is associated with breast atypia-to-carcinoma progression. NDRG1 expression might participate in the carcinogenesis and progression of invasive breast cancer. These findings provide further evidence that NDRG1 may serve as an important biomarker for invasive breast cancer.
N - myc下游调控基因1（NDRG1）已被确定为一种参与上皮细胞分化的蛋白质。作为一种新的转移抑制基因，它是否在乳腺癌致癌过程中发挥作用仍不清楚。本研究旨在阐明NDRG1在乳腺癌致癌过程中的可能作用，并进一步研究其在浸润性乳腺癌中的临床病理意义。我们通过免疫组织化学检测了NDRG1在乳腺正常上皮（n = 35）、普通导管增生（n = 22）、非典型导管增生（n = 33）、非典型小叶增生（n = 8）、导管原位癌（n = 16）、小叶原位癌（n = 6）、浸润性导管癌（n = 50）和浸润性小叶癌（n = 45）中的表达，并分析了NDRG表达与浸润性乳腺癌临床病理特征之间的相关性。进行蛋白质免疫印迹分析以研究NDRG1在20例浸润性导管癌及同一病例的配对非肿瘤组织中的表达。浸润性乳腺癌中NDRG1的表达（70/95，73.7%）高于非浸润性乳腺病变（29/85，34.1%；p < 0.05），而非浸润性乳腺病变又高于正常乳腺上皮（5/35，14.3%；p < 0.05）。统计分析显示，浸润性乳腺癌中NDRG1表达与肿瘤分期显著相关，其在浸润性导管癌中的表达明显高于浸润性小叶癌（p < 0.05）。它与年龄、绝经状态、肿瘤大小和淋巴结转移无关。蛋白质免疫印迹分析显示，浸润性导管癌中NDRG1蛋白水平明显高于同一病例的配对非肿瘤组织（p < 0.05）。NDRG - 1表达增加与乳腺非典型增生向癌的进展相关。NDRG1表达可能参与浸润性乳腺癌的发生和进展。这些发现进一步证明NDRG1可能是浸润性乳腺癌的重要生物标志物。
