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[Cancer Research 60, 1800-1804, April 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Relative Reciprocity of NRAS and PTEN/MMAC1 Alterations in Cutaneous Melanoma Cell Lines1

Hensin Tsao, Xue Zhang, Kianna Fowlkes and Frank G. Haluska2

Department of Dermatology (H. T.), Division of Hematology/Oncology (H. T., X. Z., K. F., F. G. H.), Massachusetts General Hospital and Dana-Farber/Partners CancerCare, Boston, Massachusetts 02114, and Department of Medical Genetics, China Medical University, Shenyang, People’s Republic of China (X. Z.)

Both inactivation of the tumor suppressor gene, PTEN/MMAC1, and oncogenic activation of RAS have been described in human cutaneous melanoma. In mice, activation of a RAS-containing pathway is a necessary step in the pathogenesis of murine melanomas. Because PTEN negatively regulates on the downstream effects of phosphatidylinositol-3-kinase (PI3-K), we hypothesized that the loss of PTEN/MMAC1 and the activation of RAS may be largely equivalent because RAS is a known positive upstream regulator of PI3-K. We expanded our previous survey of PTEN/MMAC1 mutations and analyzed the RAS status of 53 cutaneous melanoma cell lines, 18 glioma cell lines, and 17 uncultured cutaneous melanoma metastasis. Overall, 51% of the cell lines had alterations in either PTEN/MMAC1 or RAS. We found 16 cell lines (30%) with alterations in PTEN/MMAC1 and 11 cell lines (21%) with activating NRAS mutations; only 1 cell line had concurrent alterations in both genes. Moreover, glioma cell lines with a high frequency of PTEN/MMAC1 inactivation had no identifiable RAS alterations. Ectopic expression of PTEN in several cutaneous melanoma cell lines suppressed colony formation irrespective of PTEN/MMAC1 status; furthermore, PTEN expression in cell lines carrying activated RAS also suppressed colony formation. The relative reciprocity of PTEN/MMAC1 abrogation and NRAS activation suggests that the two genetic changes, in a subset of cutaneous melanomas, are functionally overlapping.




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