Release from quiescence stimulates the expression of integrin alpha 5 beta 1 which regulates DNA synthesis in human fibrosarcoma HT1080 cells.

Autor: Wang D; Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo 43699-0008, USA., Birkenmeier TM, Yang J, Venkateswarlu S, Humphrey L, Brattain MG, Sun L
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 1995 Sep; Vol. 164 (3), pp. 499-508.
DOI: 10.1002/jcp.1041640308
Abstrakt: We show that integrin alpha 5 subunit expression is stimulated when human fibrosarcoma HT1080 cells are released from quiescence. The alpha 5 subunit mRNA level in quiescent HT1080 cells was increased 24 hr after their release by 10% fetal bovine serum-containing medium reaching a maximum of 2.5 fold on day 2. Similar levels of induction of cell-surface alpha 5 subunit protein as well as beta 1 subunit protein were also observed. This resulted in a significant increase of cell attachment to fibronectin. The serum stimulation also increased alpha 5 subunit promoter activity by twofold which was protein synthesis independent. Subsequent deletion of alpha 5 subunit promoter DNA showed that the cis-element responsible for the activation is located between -92 bp and the transcription start site. The promoter activity was not induced until 12 hr after the release. Comparison of the effect of a serum-free medium and a 10% fetal bovine serum-supplemented medium revealed that both the DNA synthesis and alpha 5 subunit induction were independent of exogenous growth factors. The increased integrin alpha 5 beta 1 appears to function by reducing mitogenic activity since blockade of fibronectin binding to its receptor with a RGD peptide, a monoclonal anti-fibronectin antibody, or a monoclonal anti-alpha 5 subunit antibody during the release from quiescence significantly stimulated DNA synthesis. On the other hand, stable overexpression of the alpha 5 subunit resulted in decreased DNA synthesis.
Databáze: MEDLINE