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人乳腺浸润性导管癌中V型胶原α1链的过表达由转化生长因子-β1介导。

Overexpression of collagen type V α1 chain in human breast invasive ductal carcinoma is mediated by TGF-β1.

作者信息

Ren Weimin, Zhang Youyuan, Zhang Lingyun, Lin Qunbo, Zhang Jinguo, Xu Guoxiong

机构信息

Center Laboratory, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.

Department of Pathology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.

出版信息

Int J Oncol. 2018 May;52(5):1694-1704. doi: 10.3892/ijo.2018.4317. Epub 2018 Mar 15.

Abstract

Collagen type V α1 chain (COL5A1) is a minor fibrillar collagen in mammals that co-polymerizes with type I collagen to adjust the diameter of collagen molecules. However, the function of COL5A1 in invasive ductal carcinoma (IDC) of the human breast remains unknown. In the present study, our group examined the expression of COL5A1 in IDC compared with its adjacent normal tissue and fibroadenoma of the breast. COL5A1 was revealed to be overexpressed in IDC compared with benign tumor and adjacent normal control tissues, and was associated with the expression of estrogen receptor and progesterone receptor. No association between COL5A1 expression and tumor size, lymph node metastasis, clinical stage, age, or Her2 expression was identified. High expression of COL5A1 mRNA was associated with distant metastasis free survival in patients with breast cancer. Knockdown of COL5A1 led to a decrease of cell viability, as detected by the WST-1 assay, and an inhibition of migration and invasion, as detected by wound healing and Transwell assays, respectively, in the breast cancer cell line MCF-7. The expression of COL5A1 in MCF-7 cells was downregulated by transforming growth factor (TGF)‑β1, which was abolished in the presence of SB-431542, an inhibitor of TGF-β type I receptor. In conclusion, these data indicated that COL5A1 is overexpressed in IDC and regulated by TGF-β1, suggesting that an increase of COL5A1 reflects tumor progression and may serve as a novel biomarker and therapeutic target for the treatment of breast IDC.

摘要

Ⅴ型胶原蛋白α1链(COL5A1)是哺乳动物中的一种微纤维胶原蛋白,它与Ⅰ型胶原蛋白共聚以调节胶原蛋白分子的直径。然而,COL5A1在人乳腺浸润性导管癌(IDC)中的功能仍不清楚。在本研究中,我们团队检测了COL5A1在IDC中的表达,并将其与相邻正常组织及乳腺纤维腺瘤进行比较。结果显示,与良性肿瘤和相邻正常对照组织相比,COL5A1在IDC中过表达,且与雌激素受体和孕激素受体的表达相关。未发现COL5A1表达与肿瘤大小、淋巴结转移、临床分期、年龄或Her2表达之间存在关联。COL5A1 mRNA的高表达与乳腺癌患者的无远处转移生存期相关。通过WST-1检测发现,敲低COL5A1会导致细胞活力下降;通过伤口愈合实验和Transwell实验分别检测发现,敲低COL5A1会抑制乳腺癌细胞系MCF-7的迁移和侵袭。转化生长因子(TGF)-β1可下调MCF-7细胞中COL5A1的表达,而TGF-βⅠ型受体抑制剂SB-431542可消除这种下调作用。总之,这些数据表明COL5A1在IDC中过表达且受TGF-β1调控,提示COL5A1表达增加反映肿瘤进展,可能作为治疗乳腺IDC的新型生物标志物和治疗靶点。

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