Coleman A B, Lugo T G
Division of Biomedical Sciences, University of California, Riverside, USA.
J Invest Dermatol. 1998 May;110(5):793-9. doi: 10.1046/j.1523-1747.1998.00166.x.
The expression of basic fibroblast growth factor (bFGF) has been implicated as an important factor in the development of malignant melanoma. The timing of this expression suggests that bFGF plays a role early in melanoma tumor progression. Benign nevi produce bFGF, and cells cultured from these lesions show a loss of dependence on exogenous bFGF for growth. We have examined the effects of constitutive bFGF expression on the in vitro growth requirements of normal human melanocytes. bFGF was overexpressed in normal human epidermal melanocytes through genomic insertion of a human bFGF cDNA in a retroviral vector. These melanocytes produced the 18 kDa bFGF isoform as well as the higher molecular weight isoforms. The bFGF was not released into the culture medium, but it was present in the cell nucleus. The bFGF produced by these cells was mitogenic for 3T3 fibroblasts and therefore possessed functional activity; however, melanocytes producing bFGF had the same appearance and growth patterns as those infected with control virus or uninfected melanocytes. Expression of bFGF did not confer independence from the exogenous mitogen, nor would these cells form colonies in a soft-agar medium. These results indicate that expression of bFGF alone is not enough to cause aberrant growth of normal human melanocytes.
碱性成纤维细胞生长因子(bFGF)的表达被认为是恶性黑色素瘤发展中的一个重要因素。这种表达的时间表明bFGF在黑色素瘤肿瘤进展的早期起作用。良性痣产生bFGF,从这些病变中培养的细胞显示出对生长所需外源性bFGF的依赖性丧失。我们研究了组成型bFGF表达对正常人黑素细胞体外生长需求的影响。通过在逆转录病毒载体中基因组插入人bFGF cDNA,在正常人表皮黑素细胞中过表达bFGF。这些黑素细胞产生18 kDa的bFGF异构体以及更高分子量的异构体。bFGF没有释放到培养基中,但存在于细胞核中。这些细胞产生的bFGF对3T3成纤维细胞有促有丝分裂作用,因此具有功能活性;然而,产生bFGF的黑素细胞与感染对照病毒的黑素细胞或未感染的黑素细胞具有相同的外观和生长模式。bFGF的表达并没有赋予细胞对外源性有丝分裂原的独立性,这些细胞也不会在软琼脂培养基中形成集落。这些结果表明,单独的bFGF表达不足以导致正常人黑素细胞的异常生长。