Molecular correlates in the progression of normal melanocytes to melanomas

Abstract

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.