Different patterns of regulation of the genes encoding the closely related 56 kDa selenium- and acetaminophen-binding proteins in normal tissues and during carcinogenesis.
A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN-induced liver tumours in vivo. The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms.
Lanfear
J
J
Cancer Research-Campaign Beatson Laboratories, Beatson Institute for Cancer Research, Bearsden, Glasgow, UK.
Fleming
J
J
Walker
M
M
Harrison
P
P
D000082:Acetaminophen / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D051137:Selenium-Binding Proteins
D002352:Carrier Proteins; D012333:RNA, Messenger; C495176:Selenbp1 protein, mouse; C000622413:Selenbp1 protein, rat; C495177:Selenbp2 protein, mouse; D051137:Selenium-Binding Proteins; D000082:Acetaminophen