A. Platz et al., GLUTATHIONE TRANSFERASE P1-1 EXPRESSION IN HUMAN-MELANOMA METASTASES - CORRELATION TO N-RAS MUTATIONS AND EXPRESSION, Acta oncologica, 34(6), 1995, pp. 759-765
Expression of the detoxication enzyme glutathione transferase P1-1 (GS
T P1-1) at elevated levels has been noted in many types of human tumor
s, including melanomas, The products of the human II-PAS, K-PAS 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 PAS genes as w
ell as increased expression of wild-type ras proteins are common featu
res in human tumors including melanoma, We have characterized 30 melan
oma metastases from 23 melanoma patients with reference to N-RAS expre
ssion and mutation as well as to GST P1 expression (immunohistochemist
ry 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 als
o had high GST P1-1 immunoreactivity, Seven of 30 (23%) samples had lo
w N-Ras p21 immunoreactivity and no detectable N-RAS codon 61 mutation
s, Six of these 7 samples (86%) also had low GST P1-1 immunoreactivity
. The results indicate a statistically significant correlation (Spearm
an correlation coefficient, r = 0.56, p = 0.001, 2-tailed test) and pr
ovide, for the first time, indirect evidence for a possible coregulati
on of N-RAS and GST PI in human malignant melanoma which should be fur
ther evaluated.