Kondo Y, Tanaka Y, Shields J A, Kondo S
Center for Surgery Research, The Cleveland Clinic Foundation, OH 44195, USA.
Anticancer Res. 2001 Nov-Dec;21(6A):3765-72.
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.
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.
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.
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.
端粒酶是一种与多种细胞类型的细胞永生和恶性肿瘤相关的酶。另一方面，诸如碱性成纤维细胞生长因子（bFGF）或血小板衍生生长因子（PDGF）等生长因子可促进肿瘤生长，而端粒酶与这些生长因子之间的关联仍不清楚。
检测了9例视网膜母细胞瘤组织及2种细胞系（WERI-Rb-1和Y79）中的端粒酶活性以及bFGF和PDGF的表达情况。研究了端粒酶活性与bFGF或PDGF之间的关联。
在9例组织中的3例以及两种细胞系中均检测到了端粒酶活性。两个端粒酶高度阳性的组织以及WERI-Rb-1和Y79细胞表达bFGF。至于PDGF的表达，仅1例端粒酶高表达的视网膜母细胞瘤组织呈阳性。为进一步确定端粒酶活性与bFGF是否密切相关，我们抑制了它们各自的表达。使用反义处理抑制WERI-Rb-1细胞中的端粒酶，可抑制bFGF的表达，并在25至30次倍增后诱导细胞凋亡。当用中和抗体抑制bFGF表达时，端粒酶活性未受影响，也未检测到细胞凋亡。
端粒酶可能上调bFGF的表达并保护视网膜母细胞瘤细胞免于细胞死亡，这表明抑制端粒酶可能是治疗端粒酶阳性肿瘤的一种有前景的方法。
