1. Transcription of α2 Integrin Gene in Osteosarcoma Cells Is Enhanced by Tumor Promoters
- Author
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Jukka Westermarck, Veli-Matti Kähäri, Liisa Nissinen, Leeni Koivisto, and Jyrki Heino
- Subjects
Integrins ,Time Factors ,Transcription, Genetic ,Integrin alpha3 ,Integrin ,Integrin alpha2 ,CD18 ,Integrin alpha5 ,CD49c ,CD49b ,Collagen receptor ,Antigens, CD ,Okadaic Acid ,Cell Adhesion ,Tumor Cells, Cultured ,Humans ,Collagenases ,RNA, Messenger ,Osteosarcoma ,biology ,Activator (genetics) ,Integrin beta1 ,Cell Biology ,Integrin alphaV ,Blotting, Northern ,Flow Cytometry ,Molecular biology ,Up-Regulation ,Integrin alpha M ,Carcinogens ,biology.protein ,Tetradecanoylphorbol Acetate ,Integrin, beta 6 ,Collagen ,Matrix Metalloproteinase 1 - Abstract
Integrin alpha2beta1 is a heterodimeric transmembrane receptor for collagens. In osteogenic cells the expression of alpha2beta1 integrin is induced by both Kirsten sarcoma virus and chemical transformation. The association of alpha2 integrin with transformed cell phenotype was studied further by testing the effects of two tumor promoters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and okadaic acid (OA), on human MG-63 osteosarcoma cells. TPA, an activator of protein kinase C, increased the cell surface expression of alpha2 integrin and the corresponding mRNA levels. Nuclear run-on assays indicated that TPA activated the transcription of alpha2 integrin gene. TPA also slightly increased the expression of alpha3 integrin but had no effect on the transcription of alpha5, alphav, or beta1 integrin subunits. OA, an inhibitor of serine/threonine phosphatases, increased alpha2 integrin gene transcription and mRNA levels, but in contrast to TPA, OA decreased alpha3 integrin expression. The increased expression of alpha2 integrin on TPA-treated MG-63 cells led to faster cell spreading on type I collagen. Our results link the enhanced transcription of alpha2 integrin gene to tumor progression and show the independent regulation of alpha2 integrin compared to other integrin genes.
- Published
- 1998