cDNA cloning of cytochrome P-450 related to P-450p-2 from the cDNA library of human placenta. Gene structure and expression

Eur J Biochem. 1990 Jan 12;187(1):23-9. doi: 10.1111/j.1432-1033.1990.tb15273.x.

Abstract

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 omega-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 omega-hydroxylase (P-450LA omega) 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-450LA omega. 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-450LA omega, and is presumably a new member of the P-450 family including P-450p-2 and P-450LA omega. 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Blotting, Southern
  • Cloning, Molecular*
  • Cytochrome P-450 Enzyme System / genetics*
  • DNA / genetics*
  • DNA / isolation & purification
  • Exons
  • Female
  • Gene Expression*
  • Genes*
  • Humans
  • Introns
  • Molecular Sequence Data
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Organ Specificity
  • Placenta / metabolism*
  • Pregnancy
  • RNA, Messenger / genetics
  • Rabbits
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid

Substances

  • RNA, Messenger
  • DNA
  • Cytochrome P-450 Enzyme System

Associated data

  • GENBANK/X16699