Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells

Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):8928-32. doi: 10.1073/pnas.89.19.8928.

Abstract

An androgen-dependent mouse mammary carcinoma cell line (SC-3) requires androgen for growth stimulation. We have shown previously that androgen acts on SC-3 cells to induce secretion of a fibroblast growth factor (FGF)-like growth factor, which in turn stimulates growth of the cells in an autocrine manner. In this study, the androgen-induced growth factor (AIGF) was purified from a conditioned medium of SC-3 cells stimulated with testosterone. cDNA cloning of AIGF by use of its partial amino acid sequence data revealed that AIGF is a distinctive FGF-like growth factor. An AIGF cDNA (pSC17) encodes a 215-amino acid protein with a putative signal peptide, which shares 30-40% homology with known members of the FGF family. The AIGF mRNA was markedly induced by 10 nM testosterone in Northern blot analysis. Expression of AIGF cDNA in mammalian cells clearly showed remarkable stimulatory effects of AIGF on growth of SC-3 cells in the absence of androgen. Thus, it is clear that the androgen-induced growth of SC-3 cells is mediated in an autocrine manner by AIGF, which is secreted by the tumor cells themselves in response to hormonal stimuli.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division / drug effects*
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Fibroblast Growth Factor 8
  • Fibroblast Growth Factors / genetics*
  • Growth Substances / genetics
  • Growth Substances / isolation & purification
  • Growth Substances / metabolism*
  • Mammary Neoplasms, Experimental
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / metabolism*
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Testosterone / pharmacology*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Fgf8 protein, mouse
  • Growth Substances
  • Neoplasm Proteins
  • Oligodeoxyribonucleotides
  • RNA, Neoplasm
  • Recombinant Proteins
  • Fibroblast Growth Factor 8
  • Testosterone
  • Fibroblast Growth Factors

Associated data

  • GENBANK/D12482
  • GENBANK/D12483