Halaban R
Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510.
Semin Cancer Biol. 1993 Jun;4(3):171-81.
The malignant phenotype of melanocytes in vitro is characterized by growth factor autonomy, refractory to inhibitors and loss of differentiated functions. The molecular basis for these changes is not yet fully understood but it is likely to involve the inappropriate expression of specific genes that confer growth advantage due to loss and/or inactivation of tumor suppressing genes. The aberrant expression of basic fibroblast growth factor (bFGF) is one of the early and common events in melanocytic lesions, eliciting an intracellular loop of autocrine growth, dedifferentiation, but not tumorigenicity. Dysregulation of bFGF is due to gene activation probably as a result of a loss and/or inactivation of a tumor suppressor gene. A putative melanoma suppressor gene deleted in dysplastic nevi and melanomas has been recently mapped to chromosomal position 9p21. Loss of others, on chromosomes 1 and 6, has been implicated in later stages of malignant progression. Thus, further understanding the molecular basis of growth controls in melanocytes and the causes of malignant transformation is dependent on the identification of the melanoma suppressor genes and elucidation of their function.
体外黑素细胞的恶性表型具有生长因子自主性、对抑制剂不敏感和分化功能丧失的特点。这些变化的分子基础尚未完全明确，但可能涉及特定基因的不适当表达，这些基因由于肿瘤抑制基因的缺失和/或失活而赋予生长优势。碱性成纤维细胞生长因子（bFGF）的异常表达是黑素细胞病变早期常见事件之一，引发自分泌生长、去分化的细胞内循环，但不具有致瘤性。bFGF 的失调可能是由于肿瘤抑制基因的缺失和/或失活导致基因激活。最近，在发育异常痣和黑色素瘤中缺失的一个假定的黑色素瘤抑制基因已被定位到染色体 9p21 位置。在染色体 1 和 6 上其他基因的缺失与恶性进展的后期阶段有关。因此，进一步了解黑素细胞生长控制的分子基础以及恶性转化的原因取决于黑色素瘤抑制基因的鉴定及其功能的阐明。
