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Localized Aberrant Expression of Cytochrome P450 Aromatase in Primary and Metastatic Malignant Tumors of Human Liver¹

Division of Molecular Genetics (N.H., N.Y., Y.T.), Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470, Japan; and the Department of Laboratory Medicine (H.O., T.K.), Shinshu University School of Medicine, Matsumoto, Nagano 390, Japan

Address all correspondence and requests for reprints to: Nobuhiro Harada, Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470–11, Japan. nharada@fujita-hu.ac.jp.

The present study was designed to demonstrate localized aberrant expression of aromatase in primary and metastatic malignant liver tumors. Immunocytochemistry revealed the presence of locally increased aromatase protein in regions around tumors in all specimens from seven primary and seven metastatic liver tumors. This observation was further confirmed by Western blotting analysis and assay of aromatase activity in tumorous, proximal, and distal regions. Western blots showed most intensely immunoreactive bands at the position corresponding to aromatase in 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 distal tissues (1.90 ± 1.47 pmol/mg·h), in spite of a gradient decline of NADPH-cytochrome P-450 reductase activity from the distal regions to the tumors. RT-PCR analysis indicated that the aberrant increase in aromatase protein and enzyme activity in the regions proximal to tumors is caused by locally elevated aromatase messenger RNA.

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