In Vitro and In Vivo Study on the Effect of Lysosome-associated Protein Transmembrane 4 Beta on the Progression of Breast Cancer
| Autor: | Jingjing Xu, Yihong Pan, Xia Wu, Junqing Liang, Deyou Tao, Qinjie Ning, Wei Jiang, Yanting Zhou, Jing Zheng, Ying Feng, Wen Wang, Yang Zhao, Lin Zhang, Hui Wang, Ping He, Jie Yao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Tube formation Disease progression Cancer Research MMP2 business.industry Cell growth Angiogenesis LAPTM4B protein human Matrix metalloproteinase 03 medical and health sciences 030104 developmental biology 0302 clinical medicine LAPTM4B Oncology Downregulation and upregulation In vivo 030220 oncology & carcinogenesis Cancer research Medicine Original Article MCF-7 cells Breast neoplasms business |
| Zdroj: | Journal of Breast Cancer |
| ISSN: | 2092-9900 1738-6756 |
| Popis: | Purpose Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. Methods We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. Results Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. Conclusion LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|