ATP modulates PTEN subcellular localization in multiple cancer cell lines.
The tumour suppressor gene PTEN plays an important somatic role in both hereditary and sporadic breast carcinogenesis. While the role of PTEN's lipid phosphatase activity, as a negative regulator of the cytoplasmic phosphatidylinositol-3-kinase/Akt pathway is well known, it is now well established that PTEN exists and functions in the nucleus. Multiple mechanisms of regulating PTEN's subcellular localization have been reported. However none are ubiquitous across multiple cancer cell lines and tissue types. We show here that adenosine triphosphate (ATP) regulates PTEN subcellular localization in a variety of different cancer cell lines, including those derived from breast, colon and thyroid carcinomas. Cells deficient in ATP show an increased level of nuclear PTEN protein. This increase in PTEN is reversed when cells are supplemented with ATP, ADP or AMP. In contrast, the addition of the non-hydrolyzable analogue ATPgammaS, did not reverse nuclear PTEN protein levels in all the cell types tested. To our knowledge, this is the first report that describes a regulation of PTEN subcellular localization that is not specific to one cell line or tissue type, but appears to be common across a variety of cell lineages.
Lobo
Glenn P
GP
Genomic Medicine Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, NE-50, Cleveland, OH 44195, USA.
Waite
Kristin A
KA
Planchon
Sarah M
SM
Romigh
Todd
T
Houghton
Janet A
JA
Eng
Charis
C
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000378:metabolism*
D000255:Adenosine Triphosphate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human