title: Elevated expression of FGF-2 does not cause prostate cancer progression in LNCaP cells.
abstract: BACKGROUND
  Androgen-independent (AI) prostate cancer (CaP) resulting from progression of disease is untreatable. Such progression may relate to upregulation and autocrinicity of growth factor expression. We studied one candidate growth factor, basic fibroblast growth factor (FGF-2).
  
  
  METHODS
  LNCaP cells made autocrine for FGF-2 by stable transfection with FGF-2 were examined for cancer progression, measured by 1) altered response to androgen, 2) ability to grow more quickly when cocultured with bone cells in vitro or to form tumors when coinoculated with bone cells in vivo, or 3) increase in metastatic ability.
  
  
  RESULTS
  Stably transfected lines differed in FGF-2 protein expression. LNCaP-HF (high production of FGF-2) expressed more FGF-2 than LNCaP-LF (low production of FGF-2); controls were negative. In vitro, compared with LNCaPs, LNCaP-HF cells showed a slightly increased growth rate, reduced proliferation in response to androgen but not to estrogen or progesterone, and a decreased proliferative response to epidermal growth factor (EGF) and FGF-2. Although giving a slightly faster take rate, LNCaP-HF cells without Matrigel only formed small, fast-regressing tumors in male nude mice, and with Matrigel, did not differ from LNCaPs in growth rate or tumor size. No metastases occurred. No tumors grew in females. Mixed growth of FGF-2 transfectants with human fetal osteoblasts failed to cross-stimulate in vitro, or to allow tumor formation in vivo.
  
  
  CONCLUSIONS
  Although FGF-2 is overexpressed in AI CaPs, our experiments show that upregulation of FGF-2 expression is not sufficient to cause androgen independence, tumorigenicity, or metastases production (i.e., prostate cancer progression) in LNCaP cells.
authors.affiliation: Oncology Research Centre, Prince of Wales Hospital, Randwick, New South Wales, Australia. p.russell@unsw.edu.au
authors.forename: P J
authors.initials: PJ
authors.lastname: Russell
authors.forename: S
authors.initials: S
authors.lastname: Bennett
authors.forename: A
authors.initials: A
authors.lastname: Joshua
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: S R
authors.initials: SR
authors.lastname: Downing
authors.forename: M A
authors.initials: MA
authors.lastname: Hill
authors.forename: E A
authors.initials: EA
authors.lastname: Kingsley
authors.forename: R S
authors.initials: RS
authors.lastname: Mason
authors.forename: J
authors.initials: J
authors.lastname: Berry
mesh_terms: D000818:Animals; D002455:Cell Division; D013196:Dihydrotestosterone / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D013739:Testosterone / Q000494:pharmacology*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2; D013739:Testosterone