This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wei, C. Articles by Frazier, M. L. Search for Related Content PubMed PubMed Citation Articles by Wei, C. Articles by Frazier, M. L.

Mutation of Lkb1 and p53 Genes Exert a Cooperative Effect on Tumorigenesis

Departments of ¹ Epidemiology, ² Veterinary Medicine and Surgery, ³ Molecular Genetics, and ⁴ Pathology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Marsha L. Frazier, Department of Epidemiology, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3393; Fax: 713-563-0999; E-mail: mlfrazier{at}mail.mdanderson.org.

Peutz-Jeghers syndrome (PJS) is a dominantly inherited disorder characterized by gastrointestinal hamartomatous polyps and mucocutaneous melanin pigmentation. Germ line mutations in LKB1 cause PJS. We have generated mice carrying an Lkb1 exon 2 to 8 deletion by gene targeting in embryonic stem cells. Heterozygotes develop gastric hamartomas that are histologically similar to those found in humans with PJS. LKB1 is also reportedly a mediator of p53-dependent apoptosis. To explore the potential combined effects of p53 and Lkb1 alterations on tumorigenesis, we carried out a series of matings with Lkb1^+/– and p53 null mice to generate Lkb1^+/–/p53^+/– and Lkb1^+/–/p53^–/– mice. Similar to the Lkb1^+/– mice, gastrointestinal hamartomas have also been detected in the mice with these two genotypes. The Lkb1^+/–/p53^+/– mice displayed a dramatically reduced life span and increased tumor incidence compared to the mice with either Lkb1 or p53 single gene knockout. The time to onset of polyposis in Lkb1^+/–/p53^–/– mice is 2 months earlier than Lkb1^+/–/p53^+/– and Lkb1^+/– mice, whereas the latter two show a similar time to onset which is at 6 months of age. These results strongly suggested that mutations of p53 and Lkb1 gene cooperate in the acceleration of tumorigenesis. (Cancer Res 2005; 65(24): 11297-303)

This article has been cited by other articles:

				J. Dorfman and I. G. Macara STRAD{alpha} Regulates LKB1 Localization by Blocking Access to Importin-{alpha}, and by Association with Crm1 and Exportin-7 Mol. Biol. Cell, April 1, 2008; 19(4): 1614 - 1626. [Abstract] [Full Text] [PDF]

				C. Wei, C. I. Amos, N. Zhang, X. Wang, A. Rashid, C. L. Walker, R. R. Behringer, and M. L. Frazier Suppression of Peutz-Jeghers Polyposis by Targeting Mammalian Target of Rapamycin Signaling Clin. Cancer Res., February 15, 2008; 14(4): 1167 - 1171. [Abstract] [Full Text] [PDF]

				P.-Y. Zeng and S. L. Berger LKB1 Is Recruited to the p21/WAF1 Promoter by p53 to Mediate Transcriptional Activation. Cancer Res., November 15, 2006; 66(22): 10701 - 10708. [Abstract] [Full Text] [PDF]

				S. Marshall Role of Insulin, Adipocyte Hormones, and Nutrient-Sensing Pathways in Regulating Fuel Metabolism and Energy Homeostasis: A Nutritional Perspective of Diabetes, Obesity, and Cancer Sci. Signal., August 1, 2006; 2006(346): re7 - re7. [Abstract] [Full Text] [PDF]