Basic fibroblast growth factor impact on retinoblastoma progression and survival

Colleen M. Cebulla, Maria Elena Jockovich, Yolanda Piña, Hinda Boutrid, Armando Alegret, Amy Kulak, Abigail S. Hackam, Sanjoy K. Bhattacharya, William J. Feuer, Timothy G. Murray

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

PURPOSE. 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-βTag 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.

Original languageEnglish (US)
Pages (from-to)5215-5221
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number12
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Cebulla, C. M., Jockovich, M. E., Piña, Y., Boutrid, H., Alegret, A., Kulak, A., Hackam, A. S., Bhattacharya, S. K., Feuer, W. J., & Murray, T. G. (2008). Basic fibroblast growth factor impact on retinoblastoma progression and survival. Investigative Ophthalmology and Visual Science, 49(12), 5215-5221. https://doi.org/10.1167/iovs.07-1668