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

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.