Molecular mechanism of androgen-dependent growth in transformed cells. Pathway from basic science to clinical application

J Steroid Biochem Mol Biol. 1995 Jul;54(1-2):1-6. doi: 10.1016/0960-0760(95)00117-i.

Abstract

Shionogi carcinoma 115 (SC 115) has been extensively used to analyze the mechanism of androgen-dependent cancer growth. This tumor exhibits marked androgen-dependent growth in vivo and one cell line whose growth is markedly stimulated by androgen in serum-free culture condition is isolated from SC 115 tumor. This androgen-dependent growth is mediated through an induction of heparin binding growth factor termed as androgen-induced growth factor (AIGF). In addition, fibroblast growth factor receptor 1 (FGFR 1) is identified as a receptor for AIGF. The expression of FGFR 1 mRNA is up-regulated by androgen in SC 115 cells, indicating that this androgen-inducible autocrine loop is potentiated at two sites by androgen. An androgen-independent cell line is also established from this androgen-dependent SC 115 tumor. The growth of these androgen-independent cells is stimulated by AIGF, indicating that AIGF acts not only as an autocrine growth factor to androgen-dependent cells but also as a paracrine growth factor to androgen-independent cells. In addition, transfection of AIGF expression vector into androgen-dependent cells results in a facilitation of conversion from androgen-dependent to -independent phenotype. Thus, AIGF might play a role from tumor progression. These results indicate that a blockade of AIGF activity is an important therapeutic target. Actually, some compounds such as heparin and suramin are found to inhibit this androgen-induced autocrine loop. These basic observations will be discussed in relation to their possible clinical application.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Androgens / metabolism*
  • Androgens / pharmacology
  • Animals
  • Carcinoma / metabolism*
  • Cell Division / drug effects
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors*
  • Growth Substances / chemistry
  • Growth Substances / metabolism*
  • Growth Substances / pharmacology
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / pharmacology
  • Sequence Alignment
  • Suramin / pharmacology
  • Tumor Cells, Cultured

Substances

  • Androgens
  • Growth Substances
  • Neoplasm Proteins
  • Fibroblast Growth Factor 8
  • Suramin
  • Fibroblast Growth Factors