CONSTITUTIVE EXPRESSION OF MULTIPLE GROWTH-FACTOR GENES BY MELANOMA-CELLS BUT NOT NORMAL MELANOCYTES
CONSTITUTIVE EXPRESSION OF MULTIPLE GROWTH-FACTOR GENES BY MELANOMA-CELLS BUT NOT NORMAL MELANOCYTES
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DOI：
10.1111/1523-1747.ep12477822
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发表时间：
1991-07-01
影响因子：
6.5
通讯作者：
HERLYN, M
中科院分区：
文献类型：
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作者：
RODECK, U;MELBER, K;HERLYN, M
在一组转移性黑色素瘤细胞系中，我们发现了多种生长因子的稳态mRNA转录物，包括碱性成纤维细胞生长因子（bFGF）、血小板衍生生长因子（PDGF）-A、PDGF-B、转化生长因子（TGF）-β-1、TGF-α、黑色素瘤生长刺激活性（MGSA）、白细胞介素（IL）-1-α和IL-1-β，但不包括胰岛素样生长因子（IGF）-1或IGF-2。 生长因子基因的表达是组成型的，因为在RNA提取之前，黑色素瘤细胞维持在不含外源生长因子的化学成分确定的培养基中。 四种细胞系中的每一种都有两种、四种、五种或七种生长因子的单独表达模式;然而，所有细胞系都有bFGF基因的表达。 两株正常黑素细胞表达TGF-β-1，但不表达bFGF、PDGF、TGF-α或MGSA mRNA。 我们测试了黑色素瘤细胞最常表达的生长因子（bFGF、TGF-α、TGF-β、PDGF）的生长调节作用。 这些都不能持续刺激黑色素瘤细胞生长，而外源性酸活化的TGF-β在浓度> 10 ng/ml时抑制黑色素瘤生长，表明生物活性TGF-β可能代表生理生长抑制剂。 无论是PDGF或TGF-α的中和抗血清，还是表皮生长因子（EGF）受体的单克隆抗体，都不能抑制黑色素瘤细胞的生长。 我们的研究结果表明，多种生长因子的表达同时和组成的黑色素瘤细胞，但不是正常的黑色素细胞在文化。 bFGF的表达是一个共同的特征，强调了bFGF作为黑素瘤细胞自分泌因子的重要性，如前所述。 分泌的PDGF和TGF-α显然不参与黑素瘤细胞的自分泌生长刺激或不是必需的。
In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)-beta-1, TGF-alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1-alpha, and IL-1-beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF-beta-1 but not bFGF, PDGF, TGF-alpha, or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF-alpha, TGF-beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF-beta inhibited melanoma growth at concentrations > 10 ng/ml, suggesting that bioactive TGF-beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF-alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF-alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells.