TY - JOUR
T1 - Activation of distinct multidrug‐resistance (P‐glycoprotein) genes during rat liver regeneration and hepatocarcinogenesis
AU - Teeter, Larry D.
AU - Estes, Marc
AU - Chan, John Y.
AU - Becker, Frederick F.
AU - Kuo, M. Tien
AU - Atassi, Hammad
AU - Sell, Stewart
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
KW - Multidrug‐resistance genes
KW - carcinogens
KW - hepatocellular carcinoma
KW - liver cell proliferation
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U2 - 10.1002/mc.2940080202
DO - 10.1002/mc.2940080202
M3 - Article
C2 - 8104413
AN - SCOPUS:0027377964
SN - 0899-1987
VL - 8
SP - 67
EP - 73
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 2
ER -