title: Aberrant expression in multiple components of the transforming growth factor-β1-induced Smad signaling pathway during 7,12-dimethylbenz[a]anthracene-induced hamster buccal-pouch squamous-cell carcinogenesis.
abstract: Transforming growth factor (TGF)-β1 signaling controls a plethora of cellular processes including tumorigenesis. The TGF-β1 ligand initiates signaling by binding to TGF-βreceptor II (TβRII) and allowing heterodimerization with TGF-βreceptor I (TβRI); thus, TβRI is phosphorylated by TβRII. After phosphorylation, Smad2 and Smad3 heterodimerize with Smad4, and this complex migrates to the nucleus to regulate the expression of specific target genes. However, Smad7 interrupts above signal transduction by preventing phosphorylation of Smad2 or Smad3. The objective of this study was to examine the TGF-β1-induced Smad signaling pathway during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch squamous-cell carcinogenesis. Fifty 6-week-old male Syrian golden hamsters were divided into three experimental and two control groups (10 animals in each). Both pouches of each animal in the experimental groups were painted with 0.5% DMBA solution, and both pouches of each animal of one of the control groups were similarly treated with mineral oil; the other control group remained untreated throughout the experiment. Animals from three experimental groups were sacrificed at the end of 3rd, 9th, and 14th-weeks after DMBA treatment, respectively, and animals from two control groups were all sacrificed at 14th-weeks after the treatment. Immunohistochemical staining for TGF-β1, TβRI, TβRII, Smad2-4 and Smad7 were performed.
  
  
  RESULTS
  A significant increase in the expression of Smad7 and significant decreases in the expression of TβRII, Smad 2, Smad3 and Smad4 were noted during hamster buccal-pouch carcinogenesis induced by DMBA. Our findings indicate that a disruption in TGF-β1-induced Smad signaling occurs as a result of aberrant expression of multiple components in the TGF-β1 signaling pathway during DMBA-induced hamster buccal-pouch carcinogenesis, leading to loss of TGF-β1 growth-suppressive effects on transformed pouch keratinocytes.
authors.affiliation: Department of Oral Pathology, School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. k0285@ms22.hinet.net
authors.forename: Yuk-Kwan
authors.initials: YK
authors.lastname: Chen
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.forename: Anderson Hsien-Cheng
authors.initials: AH
authors.lastname: Huang
authors.forename: Shui-Sang
authors.initials: SS
authors.lastname: Hsue
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Lin
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D002610:Cheek; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic; D007150:Immunohistochemistry; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D009363:Neoplasm Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D015127:9,10-Dimethyl-1,2-benzanthracene