Transcriptional control of SPARC by v-Jun and other members of the AP1 family of transcription factors

Transformation of chick embryo fibroblasts by the v-Jun oncoprotein correla tes with a down-regulation of the extracellular matrix protein SPARC and re pression of the corresponding mRNA, Alteration in SPARC expression has been repeatedly reported in human cancers of various origin, and is thought to contribute to the remodeling of the extracellular matrix during neoplastic progression, Transcriptional control of SPARC is poorly understood, We show here that (i) v-Jun-mediated repression of the endogenous SPARC gene is en hanced by Fra2 but alleviated by ATF2, Fra2 and ATF2 being the two major pa rtners of v-Jun in the transformed cells; (ii) high basal activity as well as repression by v-Jun and modulation by Fra2 and ATF2 is restricted to a s mall proximal fragment (-124/+16) of the chicken SPARC promoter; (iii) the activity of this minimal promoter is modulated by all the AP1 family member s known in chickens (c-Jun and JunD; c-Fos and Fra2; ATF2; c-Maf, MafA, and MafB), Taken together these data demonstrate that, at least in avian prima ry cells, SPARC expression is under the control of the AP1 transcription fa ctor. Further studies with the minimal (-124/+16) promoter fragment are nee ded to understand how this control takes place at the molecular level.