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Article: Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis

TitleExpression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis
Authors
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.html
Citation
Acta Pharmacologica Sinica, 2005, v. 26 n. 10, p. 1253-1258 How to Cite?
AbstractAim: To study the expression of proline-rich Akt-substrate PRAS40 in the cell survival pathway and tumor progression. Methods: The effects of three key kinase inhibitors on PRAS40 activity in the cell survival pathway, serum withdrawal, H 2O 2 and overexpression of Akt were tested. The expression of PRAS40, Akt, Raf and 14-3-3 in normal cells and cancer cell lines was determined by Western blot. Results: The PI3K inhibitors worthmannin and Ly294002, but not rapamycin, completely inhibited the phosphorylation of Akt and PRAS40. The phosphorylation level of Akt decreased after serum withdrawal and treatment with the MEK inhibitor Uo126, but increased after treatment with H 2O 2 at low concentration, whereas none of these treatments changed PRAS40 activity. 14-3-3 is a PRAS40 binding protein, and the expression of 14-3-3, like that of PRAS40, was higher in HeLa cells than in HEK293 cells; PRAS40 had a stronger phosphorylation activity in A549 and HeLa cancer cells than in HEK293 normal cells. In the breast cancer model (MCF10A/MCF7) and lung cancer model (BEAS/H1198/H1170) we also found the same result: PRAS40 was constitutively active in H1198/H1170 and MCF7 pre-malignant and malignant cancer cells, but weakly expressed in MCF10A and BEAS normal cell. We also discussed PRAS40 activity in other NSCLC cell lines. Conclusion: The PI3K-Akt survival pathway is the main pathway that PRAS40 is involved in; PRAS40 is a substrate for Akt, but can also be activated by an Akt-independent mechanisms. PRAS40 activation is an early event during breast and lung carcinogenesis. ©2005 CPS and SIMM.
Persistent Identifierhttp://hdl.handle.net/10722/219911
ISSN
2015 Impact Factor: 3.166
2015 SCImago Journal Rankings: 1.161
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHuang, B-
dc.contributor.authorPorter, GW-
dc.date.accessioned2015-09-30T08:47:36Z-
dc.date.available2015-09-30T08:47:36Z-
dc.date.issued2005-
dc.identifier.citationActa Pharmacologica Sinica, 2005, v. 26 n. 10, p. 1253-1258-
dc.identifier.issn1671-4083-
dc.identifier.urihttp://hdl.handle.net/10722/219911-
dc.description.abstractAim: To study the expression of proline-rich Akt-substrate PRAS40 in the cell survival pathway and tumor progression. Methods: The effects of three key kinase inhibitors on PRAS40 activity in the cell survival pathway, serum withdrawal, H 2O 2 and overexpression of Akt were tested. The expression of PRAS40, Akt, Raf and 14-3-3 in normal cells and cancer cell lines was determined by Western blot. Results: The PI3K inhibitors worthmannin and Ly294002, but not rapamycin, completely inhibited the phosphorylation of Akt and PRAS40. The phosphorylation level of Akt decreased after serum withdrawal and treatment with the MEK inhibitor Uo126, but increased after treatment with H 2O 2 at low concentration, whereas none of these treatments changed PRAS40 activity. 14-3-3 is a PRAS40 binding protein, and the expression of 14-3-3, like that of PRAS40, was higher in HeLa cells than in HEK293 cells; PRAS40 had a stronger phosphorylation activity in A549 and HeLa cancer cells than in HEK293 normal cells. In the breast cancer model (MCF10A/MCF7) and lung cancer model (BEAS/H1198/H1170) we also found the same result: PRAS40 was constitutively active in H1198/H1170 and MCF7 pre-malignant and malignant cancer cells, but weakly expressed in MCF10A and BEAS normal cell. We also discussed PRAS40 activity in other NSCLC cell lines. Conclusion: The PI3K-Akt survival pathway is the main pathway that PRAS40 is involved in; PRAS40 is a substrate for Akt, but can also be activated by an Akt-independent mechanisms. PRAS40 activation is an early event during breast and lung carcinogenesis. ©2005 CPS and SIMM.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/aps/index.html-
dc.relation.ispartofActa Pharmacologica Sinica-
dc.titleExpression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis-
dc.typeArticle-
dc.identifier.emailPorter, GW: porterg@hku.hk-
dc.identifier.authorityPorter, GW=rp02099-
dc.identifier.doi10.1111/j.1745-7254.2005.00184.x-
dc.identifier.pmid16174443-
dc.identifier.scopuseid_2-s2.0-26044474979-
dc.identifier.volume26-
dc.identifier.issue10-
dc.identifier.spage1253-
dc.identifier.epage1258-
dc.identifier.isiWOS:000232346000015-
dc.publisher.placeUnited States-

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