title: Basic fibroblast growth factor impact on retinoblastoma progression and survival.
abstract: OBJECTIVE
  Chemotherapy resistance is a problem in the treatment of advanced retinoblastoma (RB). Since basic fibroblast growth factor (bFGF) is a survival factor for neural precursor cells, bFGF was evaluated as a growth and chemoresistance factor in RB.
  
  
  METHODS
  bFGF expression was analyzed in the LH-betaTag transgenic mouse model of RB and human RB cell lines by immunofluorescence, RT-PCR, and Western blot. Proliferation and apoptosis (TUNEL) assays were performed.
  
  
  RESULTS
  bFGF levels significantly increased during tumorigenesis in transgenic RB, as a function of tumor status (P = 0.005). PCR and confocal microscopy confirmed that the human cell lines and primary tumors expressed bFGF. bFGF was localized to vascular and tumor cells and rarely to glial cells. Exogenous 18-kDa bFGF induced proliferation in two RB cell lines (WERI and Y79). Western blot analysis demonstrated 34-, 22-, and 18-kDa isoforms in transgenic RB and both cell lines. In TUNEL assays, chemoresistance to carboplatin-induced apoptosis was observed in the Y79 line, which expressed a higher ratio of high (34 kDa)- to low-molecular-weight bFGF isoforms, compared with the WERI line. Similar to other bFGF tumor studies, exogenous low-molecular-weight (18 kDa) bFGF (1 ng) significantly enhanced carboplatin-induced apoptosis in the more chemosensitive WERI, but not the chemoresistant Y79 line.
  
  
  CONCLUSIONS
  RB tumors produce significant amounts of bFGF, and the differential production and response to isoforms of bFGF may have implications for invasive tumor growth and chemoresistance.
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Cebulla
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Jockovich
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Piña
authors.forename: Hinda
authors.initials: H
authors.lastname: Boutrid
authors.forename: Armando
authors.initials: A
authors.lastname: Alegret
authors.forename: Amy
authors.initials: A
authors.lastname: Kulak
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Hackam
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: William J
authors.initials: WJ
authors.lastname: Feuer
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Murray
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D016190:Carboplatin / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D012175:Retinoblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016222:Fibroblast Growth Factor 2; D016190:Carboplatin