Human cytomegalovirus glycoprotein B inhibits migration of breast cancer MDA-MB-231 cells and impairs TGF-β/Smad2/3 expression

Abstract

Breast cancer is a leading cause of cancer-associated mortality in females worldwide and evidence suggests that human cytomegalovirus (HCMV) infection may be implicated in the progress of breast cancer. HCMV glycoprotein B (gB) is the most abundant envelope protein and serves an important role in host cell entry. The present study aimed to clarify the role of HCMV gB in breast cancer cells. A HCMV gB construct (UL55) was generated and stable vUL55 gene lentivirus-transfected MDA-MB-231 cells were established. Subsequently, the effect of HCMV gB on the apoptosis and proliferation of MDA-MB-231 cells was measured by flow cytometry and Cell Counting Kit-8 assay. Furthermore, whether HCMV gB may modulate MDA-MB-231 cell migration was examined using Transwell and cell scratch assays. In addition, alterations in HCMV gB-modulated protein levels of transforming growth factor-β (TGF-β) and Mothers against decapentaplegic homologs 2/3 (Smad2/3) were detected using western blot analysis. The results indicated that UL55 cDNA was stably transfected into MDA-MB-231 cells, and that HCMV gB protein was stably expressed. No significant differences in cell apoptosis and proliferation between transfected (231-GB-OE) and negative control (231-NC) cells were observed, while the rate of cell migration was significantly decreased in the 231-GB-OE cells compared with the 231-NC cells. Additionally, the expression level of TGF-β and phosphorylation level of Smad2/3 were also decreased in 231-GB-OE cells compared with the 231-NC cells. Although certain previous studies indicated that HCMV infection was associated with breast carcinogenesis, the results of the present study indicate that the envelope protein HCMV gB exhibits no effect on cell apoptosis and proliferation, but inhibits breast cancer cell migration. This may be due to downregulated TGF-β/Smad signaling. Taken together, these studies may assist in developing anti-TGF-β agents that contribute to tumor suppression.