The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells Journal Article
| Authors: | She, Qing Bai; Solit, David B.; Ye, Qing; O'reilly, Kathryn E; Lobo, Jose; Rosen, Neal |
| Article Title: | The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells |
| Abstract: | Tumor cells with mutated PTEN proliferate in an EGFR-independent manner. Induction of PTEN sensitizes cells to EGFR inhibition, and the combination causes synergistic apoptosis. Synergy is due to inhibition of two parallel pathways that phosphorylate the proapoptotic protein BAD at distinct sites. Serine 112 phosphorylation is EGFR/MEK/MAPK dependent, whereas serine 136 phosphorylation is PI3K/Akt dependent. Either phosphorylation is sufficient to sequester BAD to 143-3. BAD is released and apoptosis is induced only if both serines are dephosphorylated in response to inhibition of both pathways. Reduction of BAD expression by RNA interference prevents apoptosis in response to pathway inhibition. Thus, BAD integrates the antiapoptotic effects of both pathways. Combined inhibition of EGFR and PI3K signaling may be a useful therapeutic strategy. |
| Keywords: | synergistic apoptosis |
| Journal Title: | Cancer Cell |
| Volume: | 8 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2005-10-01 |
| Start Page: | 287 |
| End Page: | 297 |
| Language: | English |
| ACCESSION: | BIOSIS:PREV200600044701 |
| DOI: | 10.1016/j.ccr.2005.09.006 |
| PROVIDER: | biosis |
| PMCID: | PMC3203692 |
| PUBMED: | 16226704 |
| DOI/URL: | |
| Notes: | --- - Article - "Source: Biosis" |
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