PMC:4135037 / 9601-11207 JSONTXT

{"project":"2_test","denotations":[{"id":"24531709-11158604-79171864","span":{"begin":231,"end":232},"obj":"11158604"},{"id":"24531709-11158604-79171864","span":{"begin":231,"end":232},"obj":"11158604"},{"id":"24531709-12819299-79171864","span":{"begin":231,"end":232},"obj":"12819299"},{"id":"24531709-12819299-79171864","span":{"begin":231,"end":232},"obj":"12819299"},{"id":"24531709-19620250-79171864","span":{"begin":231,"end":232},"obj":"19620250"},{"id":"24531709-19620250-79171864","span":{"begin":231,"end":232},"obj":"19620250"}],"text":"Previous studies reported that 30-50% of Men1+/− mice exhibited tumors in the endocrine pancreas, mostly insulinomas, during 8-18 months of age, and almost 80% of Men1+/− mice developed islet adenomas or carcinomas by 18-26 months 3-5. To determine the effects of Cdk4 or Cdk2 deficiency on islet tumorigenesis, we examined pancreatic tissues from 15-month-old Men1+/−; Cdk4−/− mice, Men1+/−; Cdk2−/− mice and control littermates with Men1+/+ and/or Cdk wild-type genotypes. Histological analyses showed that 62% of Men1+/−; Cdk wild-type mice (n=29) had islet tumors (Fig. 2A, C). Of the samples examined, islet adenomas were found in 12 (67%) of 18 Men1+/−; Cdk wild-type females and 6 (55%) of 11 Men1+/−; Cdk wild-type males. Essentially all islet tumors displayed insulin immunoreactivity (Fig. 2B), indicating these were insulinomas. No glucagonomas were observed in the examined groups of mice. Spontaneous islet tumors could not be found in Men1+/+ mice regardless of the Cdk4 or Cdk2 genotypes. In sharp contrast to Men1+/−; Cdk wild-type mice, none of 30 Men1+/−; Cdk4−/− mice (19 females and 11 males examined) had islet tumors or showed evidence of dysplasia. Indeed, pancreatic islets of Men1+/−; Cdk4−/− mice were markedly hypoplastic, essentially identical in appearance to the hypoplasia in the islets of Men1+/+; Cdk4−/− mice. On the other hand, 10 (77%) of 13 Men1+/−; Cdk2−/− females and 12 (57%) of 21 Men1+/−; Cdk2−/− males exhibited islet tumors, again demonstrating the lack of restraining effect of Cdk2 deficiency on both normal growth of the islets and neoplastic transformation.."}