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hTERT and TP53 deregulation in intestinal-type gastric carcinogenesis in non-human primates
Authors:Mariana Ferreira Leal  Danielle Queiroz Calcagno  André Salim Khayat  Tanielly Cristina Raiol Silva  José Augusto Pereira Carneiro Muniz  Paulo Pimentel Assumpção  Marília de Arruda Cardoso Smith  Rommel Rodríguez Burbano
Affiliation:1. Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de S?o Paulo, Rua Botucatu 740, S?o Paulo, SP, CEP 04023-900, Brazil
2. Laboratório de Citogenética Humana, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil
3. Centro Nacional de Primatas, Ministério da Saúde, Ananindeua, PA, Brazil
4. Unidade de Alta Complexidade em Oncologia, Hospital Universitário Jo?o de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil
Abstract:
Despite the high incidence, the molecular events involved in intestinal-type gastric carcinogenesis remains unclear. We previously established an intestinal-type gastric carcinogenesis model in Cebus apella, a New World monkey. In the present study, we evaluated hTERT and TP53 mRNA expression, as well as their protein immunoreactivity, in normal mucosa, non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and intestinal-type gastric cancer samples of non-human primates treated with N-methyl-nitrosourea. In addition, we evaluated the number of TP53 copies in these samples. Although hTERT immunoreactivity was only detected in gastric cancer, a continuous increase of hTERT mRNA expression was observed from non-atrophic gastritis to gastric tumors. No sample presented p53 immunoreactivity. However, we also observed a continuous decrease of TP53 mRNA expression during the sequential steps of gastric carcinogenesis. Moreover, loss of TP53 copies was observed in intestinal metaplasia and gastric cancer samples. Our study highlights that hTERT and TP53 have a key role in intestinal-type gastric cancer initiation.
Keywords:
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