Glutathione transferase P1-1 expression in human melanoma metastases: correlation to N-RAS mutations and expression.

Abstract

Expression of the detoxication enzyme glutathione transferase P1-1 (GST P1-1) at elevated levels has been noted in many types of human tumors, including melanomas. The products of the human H-RAS, K-RAS and N-RAS genes play a key role in intracellular signal transduction leading to transcriptional activation of AP-1 (Fos/Jun) responsive genes. The oncogenic mutated forms of the ras proteins are constitutively active and interfere with normal signal transduction. Mutated RAS genes as well as increased expression of wild-type ras proteins are common features in human tumors including melanoma. We have characterized 30 melanoma metastases from 23 melanoma patients with reference to N-RAS expression and mutation as well as to GST P1 expression (immunohistochemistry and genetic analysis). Twenty-three of 30 samples (70%) had high N-Ras p21 and/or N-RAS codon 61 mutations and 18 of these 23 samples also had high GST P1-1 immunoreactivity. Seven of 30 (23%) samples had low N-Ras p21 immunoreactivity and no detectable N-RAS codon 61 mutations. Six of these 7 samples (86%) also had low GST P1-1 immunoreactivity. The results indicate a statistically significant correlation (Spearman correlation coefficient, r = 0.56, p = 0.001, 2-tailed test) and provide, for the first time, indirect evidence for a possible coregulation of N-RAS and GST P1 in human malignant melanoma which should be further evaluated.

• Authors: A Platz, U Jungnelius, E Grafström, B Lagerlöf, B Mannervik, U Ringborg
• Journal: Acta oncologica (Stockholm, Sweden) (Acta Oncol) Vol. 34 Issue 6 Pg. 759-65 ( 1995) ISSN: 0284-186X [Print] England
• PMID: 7576742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Codon
• Glutathione Transferase

Topics

• Biomarkers, Tumor (genetics)
• Codon (genetics)
• Female
• Fluorescent Antibody Technique
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Genes, fos (genetics)
• Genes, jun (genetics)
• Genes, ras (genetics)
• Glutathione Transferase (genetics)
• Humans
• Male
• Melanoma (enzymology, genetics, secondary)
• Mutation (genetics)
• Signal Transduction (genetics)
• Skin Neoplasms (enzymology, genetics, secondary)
• Transcription, Genetic