TRANSCRIPTION OF ALPHA-2 INTEGRIN GENE IN OSTEOSARCOMA CELLS IS ENHANCED BY TUMOR PROMOTERS

Integrin alpha 2 beta 1 is a heterodimeric transmembrane receptor for collagens. In osteogenic cells the expression of alpha 2 beta 1 integr in is induced by both Kirsten sarcoma virus and chemical transformatio n. The association of alpha 2 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 hum an MG-63 osteosarcoma cells. TPA, an activator of protein kinase C, in creased the cell surface expression of alpha 2 integrin and the corres ponding mRNA levels. Nuclear run-on assays indicated that TPA activate d the transcription of alpha 2 integrin gene. TPA also slightly increa sed the expression of alpha 3 integrin but had no effect on the transc ription of alpha 5, alpha v, or beta 1 integrin subunits. OA, an inhib itor of serine/threonine phosphatases, increased alpha 2 integrin gene transcription and mRNA levels, but in contrast to TPA, OA decreased a lpha 3 integrin expression. The increased expression of alpha 2 integr in on TPA-treated MG-63 cells led to faster cell spreading on type I c ollagen. Our results link the enhanced transcription of alpha 2 integr in gene to tumor progression and show the independent regulation of al pha 2 integrin compared to other integrin genes. (C) 1998 Academic Pre ss.