Cancer Res  2000 Apr 1;60(7):1800-4 

Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma
cell lines.

Tsao H, Zhang X, Fowlkes K, Haluska FG.

Department of Dermatology, Massachusetts General Hospital and
Dana-Farber/Partners CancerCare, Boston 02114, USA.

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.

PMID: 10766161 [PubMed - indexed for MEDLINE]