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Activation of distinct multidrug‐resistance (P‐glycoprotein) genes during rat liver regeneration and hepatocarcinogenesis
Author(s) -
Teeter Larry D.,
Estes Marc,
Chan John Y.,
Becker Frederick F.,
Kuo M. Tien,
Atassi Hammad,
Sell Stewart
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940080202
Subject(s) - biology , p glycoprotein , hccs , gene , multiple drug resistance , messenger rna , gene expression , multidrug resistance associated protein 2 , microbiology and biotechnology , cancer research , atp binding cassette transporter , transporter , genetics , drug resistance
Abstract 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.