CDNA CLONING OF CYTOCHROME-P-450 RELATED TO P-450P-2 FROM THE CDNA LIBRARY OF HUMAN-PLACENTA - GENE STRUCTURE AND EXPRESSION

We have isolated and analyzed cDNA (designated P‐450HP cDNA) clones from a human placenta cDNA library, using the cDNA for rabbit pulmonary cytochrome P‐450P‐2, a prostaglandin ω‐hydroxylase, as a hybridization probe. The cDNA obtained encoded a polypeptide comprising 511 amino acids with a calculated molecular mass of 58987 Da, and the amino acid sequence similarity with P‐450P‐2 and rat liver laurate ω‐hydroxylase (P‐450LAω) was only about 50%. RNA blot analysis showed that the mRNA hybridizable with the human P‐450HP cDNA was inducibly expressed 3 – 5‐fold in rabbit small intestine and lung by gestation, but the expression remained constant in rabbit liver and kidney. This mode of expression was quite different from that of P‐450P‐2 and P‐450LAω. Interestingly, the mRNA hybridized with the cDNA of P‐450HP was found to be expressed in all the human tumor tissues so far examined, in sharp contrast with the facts that almost all the other species of P‐450s are known to disappear in the tumor tissues. Taken together, the deduced hemoprotein termed P‐450HP dose not seem to be the human counterpart of rabbit P‐450P‐2 or rat P‐450LAω, and is presumably a new member of the P‐450 family including P‐450P‐2 and P‐450LAω. Furthermore, the corresponding genomic DNA was also cloned and analyzed. The gene of P‐450HP spanned 18.8 kb and was separated into 11 exons by 10 introns whose locations were completely different from those of P‐450 genes so far determined. Copyright © 1990, Wiley Blackwell. All rights reserved