Association between telomerase activity and basic fibroblast growth factor up-regulation in retinoblastomas.
BACKGROUND
Telomerase is an enzyme associated with cellular immortality and malignancy in many cell types. On the other hand, growth factors such as basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF) promote tumor growth, whereas the association between telomerase and these growth factors remains unclear.


METHODS
Telomerase activity and expression of bFGF and PDGF were assayed in 9 retinoblastoma tissues and 2 cell lines (WERI-Rb-1 and Y79). The association of telomerase activity with bFGF or PDGF was investigated.


RESULTS
Telomerase activity was detected in three out of nine tissues and both cell lines. Two telomerase highly-positive tissues and WERI-Rb-1 and Y79 cells expressed bFGF. As for the expression of PDGF, only one retinoblastoma tissue with high telomerase was positive. To further determine whether telomerase activity and bFGF are closely associated, we inhibited each expression. Inhibition of telomerase in WERI-Rb-1 cells using the anti-sense treatment suppressed the expression of bFGF and subsequently induced apoptosis after 25 to 30 doublings. When bFGF expression was suppressed by the neutralizing antibody, telomerase activity was not affected nor was apoptosis detected.


CONCLUSIONS
Telomerase may up-regulate the expression of bFGF and protect retinoblastoma cells from cell death, indicating, the possibility that inhibition of telomerase is a promising approach for the treatment of telomerase-positive tumors.
Kondo
Y
Y
Center for Surgery Research, The Cleveland Clinic Foundation, OH 44195, USA. Yasuko.Kondo@mssm.edu
Tanaka
Y
Y
Shields
J A
JA
Kondo
S
S
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology; D019572:Retinal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000906:Antibodies; D010982:Platelet-Derived Growth Factor; D016372:RNA, Antisense; D016222:Fibroblast Growth Factor 2; D019098:Telomerase