Influence of basic fibroblast growth factor on the growth of HeLa cells and the expression of angiogenin

Abstract

Abstract. Basic fibroblast growth factor (bFGF) is closely involved in angiogenesis and tumor growth of various cancers, but its role in cervical cancer remains to be defined. We investigated the effects of bFGF on HeLa cell growth and studied its influence on the expression of angiogenin. We transfected the bFGF gene in the sense and antisense orientation into HeLa cells, and obtained stable bFGF underexpressing and overexpressing transfectants. In our experiments, we demonstrated that inhibition of bFGF gene and protein expression in the bFGF antisense transfectants induced increased protein expression of angiogenin. In contrast, in the bFGF sense transfectants the expression of angiogenin decreased. Delivery of recombinant angiogenin into transfected and control cells led to increased proliferation in the bFGF antisense transfectants and the control cells. However, the cell proliferation had no change in the bFGF sense transfectants. In conclusion, we demonstrated that besides its angiogenic activity, bFGF and angiogenin also directly contribute to HeLa cell proliferation. Furthermore, endogenous bFGF affects the expression of angiogenin in HeLa cells. These findings suggest that inhibition of bFGF alone is not a promising strategy to inhibit angiogenesis. IntroductionCancer of the uterine cervix is the second most common cancer among women in the world (1), and the most common gynecological malignancy in P.R. China. Angiogenesis stimulates tumor growth, invasion and metastasis, and therefore is a crucial step in tumorigenesis. Further, evidence of increased neovascularization has been shown to be a negative prognostic indicator in many solid tumors, including cervical cancer (2). Several growth factors may be involved in the angiogenic process, including angiogenin and basic fibroblast growth factor (bFGF).Angiogenin is a 14-kDa angiogenic protein originally isolated from the conditioned medium of HT-29 human colon adenocarcinoma cells (3). Angiogenin has been shown to play a role in tumor angiogenesis (4). Its expression is upregulated in many types of cancers (5-10). Angiogenin undergoes nuclear translocation in endothelial cells, which has been shown to be necessary for angiogenesis (11-13). Tsuji et al have shown that nuclear translocation of angiogenin occurred in HeLa cells regardless of the cell confluence status, and that angiogenin stimulated rRNA synthesis in HeLa nuclei (14). Many studies have focused on how angiogenin induced tumor angiogenesis and how its angiogenic activity can be disrupted. Little, however, is known about its expression and function during HeLa cell growth.Basic fibroblast growth factor (bFGF), a member of a group of heparin-binding multifunctional polypeptides, is one of the most potent angiogenic factors (15,16). It is also involved in proliferation and differentiation of a variety of normal and malignant cells and tissues (17,18). Many malignant tumors showed an increase in bFGF expression (19)(20)(21)(22). Sliutz et al have demonstrated that serum basic fibroblast growth f...

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