Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice

Loffler, K. A., Biondi, C. A., Gartside, M. G., Serewko-Auret, M. M., Duncan, R., Tonks, I. D., Mould, A. W., Waring, P., Muller, H. K., Kay, G. F. and Hayward, N. K. (2007) Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice. Oncogene, 26 27: 4009-4017. doi:10.1038/sj.onc.1210163


Author Loffler, K. A.
Biondi, C. A.
Gartside, M. G.
Serewko-Auret, M. M.
Duncan, R.
Tonks, I. D.
Mould, A. W.
Waring, P.
Muller, H. K.
Kay, G. F.
Hayward, N. K.
Title Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice
Formatted title
Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
Publication date 2007
Year available 2006
Sub-type Article (original research)
DOI 10.1038/sj.onc.1210163
Volume 26
Issue 27
Start page 4009
End page 4017
Total pages 9
Editor E. Premkumar Reddy
J. Jenkins
Place of publication London, U.K.
Publisher Nature Publishing Group
Collection year 2008
Language eng
Subject 321015 Oncology and Carcinogenesis
C1
730108 Cancer and related disorders
Abstract To identify possible genetic interactions between the mechanisms of tumor suppression of menin and pRb, we intercrossed mice with targeted deletions of Men1 and Rb1, and compared tumor development in cohorts of animals carrying single or dual mutations of these tumor-suppressor genes. In mice lacking one copy of Men1, pancreatic islet and anterior pituitary adenomas are common. In animals lacking one copy of Rb1, intermediate pituitary and thyroid tumors occur at high frequency, with less frequent development of pancreatic islet hyperplasia and parathyroid lesions. In mice heterozygous for both Men1 and Rb1, pancreatic hyperplasia and tumors of the intermediate pituitary and thyroid occurred at high frequency. Serum measurements of calcium and glucose did not vary significantly between genotypic groups. Loss of heterozygosity at the Rb1 locus was common in pituitary and thyroid tumors, whereas loss of menin was observed in pancreatic and parathyroid lesions. The tumor spectrum in the double heterozygotes was a combination of pathologies seen in each of the individual heterozygotes, without decrease in age of onset, indicating independent, non-additive effects of the two mutations. Together with the lack of increased tumor spectrum, this suggests that menin and pRb function in a common pathway of tumor suppression.
Keyword endocrine
pancreas
pituitary
parathyroid
thyroid
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Fri, 02 May 2008, 14:13:07 EST by Brenda Mason on behalf of Medicine - Royal Brisbane and Women's Hospital