LOCALIZED ABERRANT EXPRESSION OF CYTOCHROME-P450 AROMATASE IN PRIMARYAND METASTATIC MALIGNANT-TUMORS OF HUMAN LIVER

The present study was designed to demonstrate localized aberrant expre ssion of aromatase in primary and metastatic malignant liver tumors. I mmunocytochemistry revealed the presence of locally increased aromatas e protein in regions around tumors in all specimens from seven primary and seven metastatic liver tumors. This observation was further confi rmed by Western blotting analysis and assay of aromatase activity in t umorous, proximal, and distal regions. Western blots showed most inten sely immunoreactive bands at the position corresponding to aromatase i n proximal tissues where aromatase activities also were higher (2.75 /- 1.59 pmol/mg.h) than in tumors (0.137 +/- 0.115 pmol/mg.h) and dist al tissues (1.90 +/- 1.47 pmol/mg.h), in spite of a gradient decline o f NADPH-cytochrome P-450 reductase activity from the distal regions to the tumors. RT-PCR analysis indicated that the aberrant increase in a romatase protein and enzyme activity in the regions proximal to tumors is caused by locally elevated aromatase messenger RNA.