Marked heterogeneity of aromatase activity in human malignant melanoma tissue.
The prognosis from human malignant melanoma varies according to sex and to multiple histologic, biologic and cell kinetic parameters. Thus melanomas exhibit a major degree of heterogeneity in their biologic properties and further characterization of their biochemical heterogeneity should yield important information. The present study sought to demonstrate the activity of a biochemical marker of estrogen synthesis, the aromatase enzyme, in melanoma tissue and to determine its range of activity. Initially, we validated a highly sensitive radiometric assay for aromatase by comparing it with a direct product isolation method. We detected production of 417 pmol/g protein/h of estrone and 37.3 pmol/g protein/h of estradiol by direct product isolation in a human melanoma and 398 pmol estrone/g protein/h by the radiometric assay. The activity present was blocked by similar amounts of the aromatase inhibitor, aminoglutethimide, as were necessary to block placental, breast cancer, and rat brain aromatase activity. We then assayed aromatase radiometrically in 19 human melanomas and found measurable activity ranging from 9 to 398 pmol estrone/g protein/h in 15 tissues. No relationship with the patient's age or sex was demonstrated. The activity exceeded by 2-fold that previously detected in 49/61 human breast cancers. This study identified a marker enzyme in melanoma tissue which varied by 40-fold among human tumors. Correlation of aromatase activity with prognosis and response to various types of therapy is now necessary to establish the biologic relevance of this finding.
Santen
R J
RJ
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University 17033.
Santner
S J
SJ
Harvey
H A
HA
Lipton
A
A
Simmonds
M
M
Feil
P D
PD
Manders
E
E
Davis
T S
TS
D000328:Adult; D000368:Aged; D000616:Aminoglutethimide / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor / Q000032:analysis*; D004958:Estradiol / Q000096:biosynthesis; D004970:Estrone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology*; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000616:Aminoglutethimide; D004970:Estrone; D004958:Estradiol; D001141:Aromatase