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10.1111/j.1349-7006.2001.tb01042.x

http://scihub22266oqcxt.onion/10.1111/j.1349-7006.2001.tb01042.x
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suck abstract from ncbi


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pmid11173539
      Jpn+J+Cancer+Res 2001 ; 92 (1 ): 16-22
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  • Alterations of the transforming growth factor-beta signaling pathway in hepatocellular carcinomas induced endogenously and exogenously in rats #MMPMID11173539
  • Sasaki Y ; Tsujiuchi T ; Murata N ; Tsutsumi M ; Konishi Y
  • Jpn J Cancer Res 2001[Jan]; 92 (1 ): 16-22 PMID11173539 show ga
  • To elucidate involvement of the transforming growth factor-beta (TGF-beta) signaling pathway in endogenous and exogenous liver carcinogenesis, we investigated mutations of TGF-beta receptor type II (TGF-betaRII), Smad2 and Smad4 genes, and expression of TGF-betaRII in hepatocellular carcinomas (HCCs) induced by a choline-deficient L-amino acid-defined (CDAA) diet and by N-nitrosodiethylamine (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-betaRII, Smad2 and Smad4 were investigated by reverse transcription (RT)-polymerase chain reaction (PCR)-restriction-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-betaRII or Smad4 alterations. No mutations of TGF-betaRII, Smad2 and Smad4 were encountered in eleven HCCs induced by the exogenous carcinogen. Semi-quantitative RT-PCR revealed reduced expression of TGF-betaRII 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-beta signaling pathway may be disturbed in endogenous liver carcinogenesis in rats.
  • |Alkylating Agents [MESH]
  • |Animals [MESH]
  • |Carcinoma, Hepatocellular/etiology/*genetics [MESH]
  • |Choline [MESH]
  • |DNA-Binding Proteins/genetics [MESH]
  • |Diethylnitrosamine [MESH]
  • |Liver Neoplasms/etiology/*genetics [MESH]
  • |Male [MESH]
  • |Polymorphism, Single-Stranded Conformational [MESH]
  • |Rats [MESH]
  • |Rats, Inbred F344 [MESH]
  • |Reverse Transcriptase Polymerase Chain Reaction [MESH]
  • |Signal Transduction/*genetics [MESH]
  • |Smad2 Protein [MESH]
  • |Smad4 Protein [MESH]
  • |Trans-Activators/genetics [MESH]


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