Document Detail

Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines.
MedLine Citation:
PMID:  10766161     Owner:  NLM     Status:  MEDLINE    
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.
H Tsao; X Zhang; K Fowlkes; F G Haluska
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  60     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-04     Completed Date:  2000-05-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1800-4     Citation Subset:  IM    
Department of Dermatology, Massachusetts General Hospital and Dana-Farber/Partners CancerCare, Boston 02114, USA.
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MeSH Terms
Alternative Splicing
Amino Acid Sequence
Base Sequence
Brain Neoplasms / genetics
Frameshift Mutation
Gene Deletion
Genes, Tumor Suppressor*
Genes, ras*
Glioma / genetics
Melanoma / genetics*
Melanoma, Experimental / genetics
PTEN Phosphohydrolase
Phosphoric Monoester Hydrolases / genetics*
Point Mutation
Proto-Oncogene Proteins p21(ras) / genetics
Sequence Deletion
Skin Neoplasms / genetics*
Tumor Cells, Cultured
Tumor Suppressor Proteins*
Reg. No./Substance:
0/Tumor Suppressor Proteins; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC protein, human; EC Phosphohydrolase; EC protein, human; EC Proteins p21(ras)

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