Activation of distinct multidrug-resistance (P-glycoprotein) genes during rat liver regeneration and hepatocarcinogenesis.
The multidrug transporter P-glycoproteins are encoded by three multidrug-resistance (mdr) genes in rodents, designated mdr1a (mdr3), mdr1b (mdr1), and mdr2. Only the first two genes are functionally related to multidrug resistance. Activation of rodent mdr genes during liver regeneration and hepatocarcinogenesis has been reported. In mice, mdr1a is activated in hepatocellular carcinomas (HCCs) produced by various carcinogenic protocols, whereas both mdr1a and mdr2 are activated during liver regeneration. In this communication, we report isolating three gene-specific probes for the rat mdr homologues, which were used as probes in an RNase protection assay to demonstrate that mdr1b mRNA was expressed in HCCs induced by two different protocols. Furthermore, high levels of hepatic mdr1b mRNA but only moderate levels of mdr1a and mdr2 mRNA were seen in preneoplastic lesions in rats treated with 2-acetylaminofluorene. Likewise, highly elevated levels of hepatic mdr1b mRNA but only moderately increased levels of mdr1a and mdr2 mRNA were seen after partial hepatectomy. Nevertheless, the general patterns of tissue-specific expression of these three mdr genes were similar in rats and mice. These results reveal a complex hepatic gene expression pattern during hepatocarcinogenesis and hepatic proliferation for this conserved gene family in rodents.
Teeter
L D
LD
Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Estes
M
M
Chan
J Y
JY
Atassi
H
H
Sell
S
S
Becker
F F
FF
Kuo
M T
MT
D015073:2-Acetylaminofluorene; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000737:chemistry; D004052:Diethylnitrosamine; D004351:Drug Resistance / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene