Publication Date:
2009-09-05
Description:
PTEN (phosphatase and tensin homolog on chromosome 10) is a tumor suppressor whose cellular regulation remains incompletely understood. We identified phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) as a PTEN-interacting protein. P-REX2a mRNA was more abundant in human cancer cells and significantly increased in tumors with wild-type PTEN that expressed an activated mutant of PIK3CA encoding the p110 subunit of phosphoinositide 3-kinase subunit alpha (PI3Kalpha). P-REX2a inhibited PTEN lipid phosphatase activity and stimulated the PI3K pathway only in the presence of PTEN. P-REX2a stimulated cell growth and cooperated with a PIK3CA mutant to promote growth factor-independent proliferation and transformation. Depletion of P-REX2a reduced amounts of phosphorylated AKT and growth in human cell lines with intact PTEN. Thus, P-REX2a is a component of the PI3K pathway that can antagonize PTEN in cancer cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936784/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936784/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fine, Barry -- Hodakoski, Cindy -- Koujak, Susan -- Su, Tao -- Saal, Lao H -- Maurer, Matthew -- Hopkins, Benjamin -- Keniry, Megan -- Sulis, Maria Luisa -- Mense, Sarah -- Hibshoosh, Hanina -- Parsons, Ramon -- CA097403/CA/NCI NIH HHS/ -- P01 CA097403/CA/NCI NIH HHS/ -- P01 CA097403-01A10003/CA/NCI NIH HHS/ -- P01 CA097403-06A1/CA/NCI NIH HHS/ -- R01 CA082783/CA/NCI NIH HHS/ -- R01 CA082783-06/CA/NCI NIH HHS/ -- R01 CA082783-07/CA/NCI NIH HHS/ -- R01 CA082783-08/CA/NCI NIH HHS/ -- R01 CA082783-09/CA/NCI NIH HHS/ -- R01 CA082783-10/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2009 Sep 4;325(5945):1261-5. doi: 10.1126/science.1173569.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729658" target="_blank"〉PubMed〈/a〉
Keywords:
Breast Neoplasms/genetics/metabolism/pathology
;
Cell Line
;
Cell Line, Tumor
;
Cell Proliferation
;
Female
;
GTPase-Activating Proteins/genetics/*metabolism
;
Guanine Nucleotide Exchange Factors
;
Humans
;
Male
;
Mutation
;
Neoplasms/genetics/*metabolism/pathology
;
PTEN Phosphohydrolase/*antagonists & inhibitors/chemistry/genetics/*metabolism
;
Phosphatidylinositol 3-Kinases/*metabolism
;
Phosphorylation
;
Protein Binding
;
Protein Structure, Tertiary
;
Proto-Oncogene Proteins c-akt/metabolism
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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