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

$48.00 plus tax (Refund Policy)

Download / Buy Article:

Abstract:

Abstract Aim:

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, H2O2 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 H2O2 at low concentration, whereas none of these treatments changed PRAS40 activity. 14-3-3 is a PRAS40 binding protein, nd 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 premalignant 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 Aktindependent mechanisms. PRAS40 activation is an early event during breast and lung carcinogenesis.

Keywords: 14-3-3 protein; PI3K-Akt pathway; PRAS40; kinase inhibitors

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2005.00184.x

Affiliations: 1: Department of Biological Science, Anhui University School of Life Science, Hefei, Anhui 230039, China; 2: Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30032, USA

Publication date: October 1, 2005

Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more