Transduction of the SkBr3 breast carcinoma cell line with the HOXB7 gene induces bFGF expression, increases cell proliferation and reduces growth factor dependence

Oncogene. 1998 Jun 25;16(25):3285-9. doi: 10.1038/sj.onc.1201875.

Abstract

Several melanomas, carcinomas, glioblastomas and leukemias showed coordinated expression of HOXB7 and bFGF with exception of the SkBr3 mammary carcinoma that was negative for both. Transduction of HOXB7 gene into SkBr3 cells, induced bFGF expression, increased growth rate, independence from serum withdrawal and ability to form colonies in semisolid medium. ELISA assay showed that most of bFGF was associated to cell lysate when cells were cultured at 1% serum whereas in cells kept to 10% serum bFGF was detected both within cell lysate or secreted into cell supernatants. Antisense oligos to bFGF inhibited the growth of cells cultured in 1%, indicating that beside the possible activation of additional genes other than bFGF by HOXB7 transduction, only bFGF induction accounts for the observed results. Moreover, since inhibition of cell proliferation occurred in cells kept in 1% but not 10% serum, a bFGF intracrine loop appears operative in serum starved SkBr3/HOXB7 cells. Also, these results further indicate bFGF as target of HOXB7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agar / pharmacology
  • Breast Neoplasms / genetics*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Culture Media / pharmacology
  • Culture Media, Conditioned / chemistry
  • Culture Media, Serum-Free / pharmacology
  • Female
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / genetics*
  • Fibroblast Growth Factor 2 / metabolism
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic
  • Genes, Homeobox / genetics*
  • Growth Substances / pharmacology
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Transfection
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / metabolism

Substances

  • Culture Media
  • Culture Media, Conditioned
  • Culture Media, Serum-Free
  • Growth Substances
  • HOXB7 protein, human
  • Homeodomain Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Fibroblast Growth Factor 2
  • Agar