TY - JOUR
T1 - Genetic background controls tumor development in Pten-deficient mice
AU - Freeman, Dan
AU - Lesche, Ralf
AU - Kertesz, Nathalie
AU - Wang, Shungyou
AU - Li, Gang
AU - Gao, Jing
AU - Groszer, Matthias
AU - Martinez-Diaz, Hilda
AU - Rozengurt, Nora
AU - Thomas, George
AU - Liu, Xin
AU - Wu, Hong
PY - 2006/7/1
Y1 - 2006/7/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-05-4143
DO - 10.1158/0008-5472.CAN-05-4143
M3 - Article
C2 - 16818619
AN - SCOPUS:33746154235
SN - 0008-5472
VL - 66
SP - 6492
EP - 6496
JO - Cancer Research
JF - Cancer Research
IS - 13
ER -