title: Aberrant activation of Wnt/β-catenin signaling pathway contributes to the sequential progression of DMBA-induced HBP carcinomas.
abstract: Wnt signaling pathway mediated via interactions between β-catenin and members of the TCF/LEF-1 family of transcription factors plays a central role in the regulation of epithelial cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition, and invasion. Aberrant activation of the Wnt/β-catenin signaling pathway with overexpression of Wnt and Fz, mutations of APC, β-catenin, and axin 1, and cytoplasmic accumulation of β-catenin have been frequently reported in a broad spectrum of human malignancies including oral squamous cell carcinomas (OSCCs). However, changes in the components of the Wnt signaling pathway have not been documented during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis, a paradigm for oral oncogenesis and chemointervention. In this study, we evaluated the role of β-catenin accumulation and Wnt ligands, Wnt signaling members (Fz, Dvl, APC, GSK-3β, axin, and WIF) and the downstream targets of Wnt (cyclin D1, MMP-2, and MMP-9) during the sequential progression of DMBA-induced HBP carcinomas by semi-quantitative RT-PCR and western blot analyses. Our data reveal a correlation between β-catenin accumulation and activation of Wnt signaling, and its downstream effector molecules during the sequential development of HBP carcinomas from hyperplasia to invasive carcinoma through dysplasia. Our data also support a pivotal role for β-catenin in the malignant transition of the HBP. Aberrant Wnt signaling may be a hallmark of progression to malignancy during DMBA-induced HBP carcinogenesis and could be a potential preventive and therapeutic target for suppression of OSCC.
authors.affiliation: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.
authors.forename: Ramamurthi
authors.initials: R
authors.lastname: Vidya Priyadarsini
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Senthil Murugan
authors.forename: Siddavaram
authors.initials: S
authors.lastname: Nagini
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D002610:Cheek; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D051153:Wnt Proteins; D051176:beta Catenin; D015127:9,10-Dimethyl-1,2-benzanthracene