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• W2045340285 abstract "To elucidate involvement of the transforming growth factor-β (TGF-β) signaling pathway in endogenous and exogenous liver carcinogenesis, we investigated mutations of TGF-β receptor type II (TGF-βRII), Smad2 and Smad4 genes, and expression of TGF-βRII in hepatocellular carcinomas (HCCs) induced by a choline-deficient L-amino acid-defined (CDAA) diet and by N-nitrosodiethyl-amine (DEN). Male Fischer 344 rats received a CDAA diet continuously and HCCs were sampled after 75 weeks. Administration of DEN was followed by partial hepatectomy (PH), with colchicine to induce cell cycle disturbance and a selection pressure regimen, HCCs being obtained after 42 weeks. Total RNAs were extracted from individual HCCs and mutations in TGF-PRH, Smad2 and Smad4 were investigated by reverse transcription (RT)-polymerase chain reaction (PCR)-restric-tion-single-strand conformation polymorphism (SSCP) analysis followed by sequencing analysis. Mutations of Smad2 were detected in 2 out of 12 HCCs (16.7%) induced by the CDAA diet, a GGT-to-GGC transition (Gly to Gly) at codon 30 and a TCT-to-GCT (Ser to Ala) transversion at codon 118, without any TGF-βRII or Smad4 alterations. No mutations of TGF-βRII, Smad2 and Smad4 were encountered in eleven HCCs induced by the exogenous carcinogen. Semi-quantitative RT-PCR revealed reduced expression of TGF-βRII in 2 HCCs (16.7%) without Smad2 mutations out of 12 HCCs induced by the CDAA diet and none of 11 induced by DEN. These results suggest that the TGF-p signaling pathway may be disturbed in endogenous liver carcinogenesis in rats." @default.
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• W2045340285 date "2001-01-01" @default.
• W2045340285 modified "2023-10-16" @default.
• W2045340285 title "Alterations of the Transforming Growth Factor-(β Signaling Pathway in Hepatocellular Carcinomas Induced Endogenously and Exogenously in Rats" @default.
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• W2045340285 doi "https://doi.org/10.1111/j.1349-7006.2001.tb01042.x" @default.
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