Steroid hormone-dependent overexpression of cytochromes P450 2A in liver tumors of TGF alpha transgenic male mice.
To clarify the mechanism underlying the male preference of liver tumor in transforming growth factor (TGF) alpha transgenic mice, we analyzed the sexually dimorphic expression of two P450s, i.e., female-specific mouse 15 alpha hydroxylase P450 (2A4) and coumarin 7-hydroxylase P450 (2A5). The expression of 2A4 mRNA in the livers of both transgenic and nontransgenic males was low compared with that in females. P450 2A5 mRNA in the transgenic males was slightly elevated in the adjacent non-tumorous tissues and dramatically elevated in the tumor compared with that in nontransgenic male liver. The activity of P450 2A5 was higher in females than in males in control and transgenic mice but the difference was smaller in the transgenic mice. The activity of P450 2A5 was exceptionally high in liver tumors of transgenic males, as indicated by mRNA expression. These results suggest that female-specific P450 2A5 is induced in the livers of TGF alpha transgenic male mice, particularly in liver tumors of transgenic male mice overexpressing TGF alpha, and may be useful as a marker for mouse hepatocarcinogenesis.
Takagi
H
H
First Department of Internal Medicine, Gunma University School of Medicine, Japan.
Aida
K
K
Sohara
N
N
Mori
M
M
Merlino
G
G
Negishi
M
M
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor; D015152:Blotting, Northern; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D012727:Sex Characteristics; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; C050356:steroid 15-alpha-hydroxylase