hTERT and TP53 deregulation in intestinal-type gastric carcinogenesis in non-human primates.
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.
Mariana Ferreira
MF
Leal
Danielle Queiroz
DQ
Calcagno
André Salim
AS
Khayat
Tanielly Cristina Raiol
TC
Silva
José Augusto Pereira Carneiro
JA
Muniz
Paulo Pimentel
PP
Assumpção
Marília
M
de Arruda Cardoso Smith
Rommel Rodríguez
RR
Burbano
D000818:Animals; D063646:Carcinogenesis; D002428:Cebus; D005753:Gastric Mucosa / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000473:pathology; D023421:Models, Animal; D011230:Precancerous Conditions / Q000473:pathology*; D018419:Primate Diseases / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D019098:Telomerase