Experimental oral carcinoma of the tongue and buccal mucosa: possible biologic markers linked to cancers at two anatomic sites.
ABSTRACT The application of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) can initiate and promote the development of oral squamous cell carcinoma of the tongue and buccal mucosa. In this study the level of expression of various markers related to the development of programmed cell death (PCD) in the respective oral carcinomas was analyzed. Sixteen male and female Syrian hamsters (Mesocrietus auratus) were treated with 0.05% DMBA for 16 weeks. Immunohistochemistry was used to observe the expression of p53, proliferating cell nuclear antigen (PCNA), Bcl-2, and nucleosome formation. Single-strand conformational polymorphism (SSCP) for exons 2-9 and sequence analysis of exon 9 of the p53 gene from normal buccal or tongue mucosa as well as the squamous cell carcinomas from the buccal mucosa or the tongue were determined. p53 (wild type) expression was significantly reduced in the tongue dysplastic mucosa or squamous cell carcinoma. The SSCP disclosed banding shifts or new bands in exons 2/3, 4, 8, and 9 for the tongue or buccal oral carcinomas (five of each). In exon 9 the mutation in codon 307 (ala)GCC-GTC(val) was present in the tongue but not in the buccal carcinoma. Other markers included the level of PCNA. PCNA was initially lower in the premalignant tongue lesions but increased in oral squamous cell carcinoma at both sites. In contrast, the amount of nucleosome formation in the tongue carcinomas was less than the level noted for buccal cancers but premalignant dysplasias in the tongue mucosa exhibited higher levels. The inhibitor of PCD, Bcl-2 was lower for dysplasias and carcinomas of the tongue compared to similar lesions of the buccal mucosa. These results indicate that oral carcinomas of different anatomical sites can exhibit differences in growth, oncogene mutation expression, and the development of PCD. The differences in Bcl-2 and nucleosome formation may signify their influence on oncogene expression and growth potential for developing transformed clones and established oral carcinomas.
SourceAvailable from: Gaurav Kumar
Dataset: JEPTO 2012 - Gaurav Kumar
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ABSTRACT: Galectin-3 (Gal3) has been implicated in the development of different tumors because of its involvement in the Wnt signaling pathway by promoting beta-catenin translocation into the nucleus. The APC protein, a negative regulator of this pathway, has been strongly implicated in the development of colon cancer, but still has an undetermined role in the formation of oral cancer. Therefore, this study aimed to evaluate the relationship between Gal3, the Wnt signaling pathway, and APC expression in dysplasias and carcinomas developed experimentally in mice. Sixty galectin-3-deficient (Gal3(-/-)) and 60 wild-type (Gal3(+/+)) mice were early employed to be treated with the carcinogen 4NQO for 16 weeks and killed at either week 16 or week 32. Tongues were removed, processed and embedded in paraffin blocks. Sections 5 μm thick were made, and then stained by H&E to establish the diagnosis of dysplasia and carcinoma. Sections of 2 μm thickness were made to detect APC expression in these lesions by immunohistochemistry. Oral carcinogenesis occurred in both groups of mice, but no statistical difference was reached. APC expression was exclusively seen in the cytoplasm of all lesions studied. In the intragroup analysis, the majority of dysplasias and carcinomas exhibiting higher APC immunoreactivity was observed in Gal3(-/-) mice compared to Gal3(+/+) mice, but no significant difference was found. However, a statistical difference was only observed between dysplastic lesions from two mice. Our results showed that neither the absence of Gal3 nor the APC protein appears to play a role in malignant transformation of the tongue.
International Journal of Morphology 06/2006; 24(2):231-238. · 0.20 Impact Factor