Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene

Citation
Eb. Gil et al., Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene, P NAS US, 96(6), 1999, pp. 2925-2930
Citations number
38
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
6
Year of publication
1999
Pages
2925 - 2930
Database
ISI
SICI code
0027-8424(19990316)96:6<2925:ROTIDP>2.0.ZU;2-M
Abstract
The human PTEN tumor suppressor gene is mutated in a wide variety of sporad ic tumors. To determine the function of PTEN in vivo we have studied a PTEN homolog in Caenorhabditis elegans, We have generated a strong loss-of func tion allele of the PTEN homolog and shown that the deficient strain is unab le to enter dauer diapause, An insulin-like phosphatidylinositol 3-OH kinas e (PI3'K) signaling pathway regulates dauer-stage entry. Mutations in eithe r the daf-2 insulin receptor-like (IRL) gene or the age-1 encoded PI3'K cat alytic subunit homolog cause constitutive dauer formation and also affect t he life span, brood size, and metabolism of nondauer animals. Strikingly, l oss-of-function mutations in the age-1 PI3'K and daf-2 IRL genes are suppre ssed by loss-of-function mutations in the PTEN homolog, me establish that t he PTEN homolog is encoded by daf-18, a previously uncloned gene that has b een shown to interact genetically with the DAF-2 IRL AGE-1 PI3'K signaling pathway, This interaction provides clear genetic evidence that PTEN acts to antagonize PI3'K function in vivo, Given the conservation of the PI3'K sig naling pathway between C. elegans and mammals, the analysis of daf-18 PTEN mutant nematodes should shed light on the role of human PTEN in the etiolog y of metabolic disease, aging, and cancer.