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Progression to steroid autonomy is accompanied by altered sensitivity to growth factors in S115 mouse mammary tumour cells

Abstract

Progression to steroid autonomy is a major clinical problem in the treatment of steroid-sensitive tumours. Molecular mechanisms remain unknown but recent hypotheses imply a role for growth factors in this progression. Since S115 + A androgen-responsive mouse mammary tumour cells provide a model system to study this phenomenon in vitro, we have used this model to investigate growth factor gene expression and sensitivity during progression from a steroid sensitive to insensitive state. S115 + A androgen-responsive cells showed a positive proliferative response, morphological response and increased saturation density to various forms of fibroblast growth factor (FGF) and transforming growth factor beta (TGF beta) in both monolayer and suspension culture. A marked synergy was noted, however, between FGF and TGF beta in promoting growth in suspension culture. S115 + A cells possessed mRNA for both acidic FGF (aFGF) and TGF beta 1, both of which were increased by testosterone. Progression to androgen insensitivity was associated with a reversal of growth factor response such that all growth factor responses became generally inhibitory on growth of the unresponsive cells but with a particularly striking synergistic action between FGF and TGF beta 1 on inhibition of both monolayer and suspension growth. Levels of aFGF and TGF beta 1 mRNAs remained low in steroid-insensitive S115-A cells, indicating that loss of response was not associated with any constitutive upregulation of endogenous production of one of these growth factors. The scientific and clinical implications are discussed.

Type Journal
ISBN 0960-0760 (Print)
Authors Daly, R. J.;Carrick, N.;Darbre, P. D. :
Publisher Name J STEROID BIOCHEM
Published Date 1995-01-01 00:00:00
Published Volume 54
Published Issue 1-2
Published Pages 21-9
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7632611
Status Published In-print