Genetic background controls tumor development in Pten-deficient mice

Dan Freeman, Ralf Lesche, Nathalie Kertesz, Shungyou Wang, Gang Li, Jing Gao, Matthias Groszer, Hilda Martinez-Diaz, Nora Rozengurt, George Thomas, Xin Liu, Hong Wu

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. Germ line mutations of PTEN have been detected in three rare autosomal-dominant disorders. However, identical mutations in the PTEN gene may lead to different symptoms that have traditionally been described as different disorders, such as Cowden disease, Lhermitte-Duclos disease, and Bannayan-Zonana syndromes. This lack of genotype-phenotype correlation prompted us to directly test the possible effects of genetic background or modifier genes on PTEN-controlled tumorigenesis using genetically engineered mouse models. In this study, we generated two animal models in which either exon 5 (Pten Δ5) or promoter to exon 3 (Pten-) of the murine Pten gene were deleted and compared phenotypes associated with individual mutations on two genetic backgrounds. We found that the onset and spectrum of tumor formation depend significantly on the genetic background but less on the type of mutation generated. Our results suggest that PTEN plays a critical role in cancer development, and genetic background may influence the onset, the spectrum, and the progression of tumorigenesis caused by Pten mutation.

Original languageEnglish (US)
Pages (from-to)6492-6496
Number of pages5
JournalCancer Research
Volume66
Issue number13
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Freeman, D., Lesche, R., Kertesz, N., Wang, S., Li, G., Gao, J., Groszer, M., Martinez-Diaz, H., Rozengurt, N., Thomas, G., Liu, X., & Wu, H. (2006). Genetic background controls tumor development in Pten-deficient mice. Cancer Research, 66(13), 6492-6496. https://doi.org/10.1158/0008-5472.CAN-05-4143