Pancreatic Disorders & Therapy
Open Access
ISSN: 2165-7092
+44 1478 350008
ISSN: 2165-7092
+44 1478 350008
Hem D Shukla
University of Maryland, USA
Johns Hopkins University, USA
Posters & Accepted Abstracts: Pancreat Disord Ther
In the present investigation the proteomic analysis of oxidatively stressed BxPC3 human pancreatic cancer cells have shown the elevated level of a6b4 integrin, caveolin-1, K-RAS, EGFR, annexin A4 and annexin A11 as compared to HPDE control. The high throughput proteomic and bioinformatic analysis by protein center and ingenuity pathway analysis have shown the altered integrin signaling pathway and MAPK pathway in pancreatic ductal adenocarcinoma cell line. Further, the activation of NRF2 transcriptional factor in BxPC-3 exposed to extreme oxidative stress shows that it may bind to the DNA at the location of the hARE (human antioxidant response element) which is the master regulator of the total antioxidant system. It seems likely that upon exposure of cells to oxidative stress, Nrf2 is phosphorylated in response to protein kinase C, phosphatidylinositol 3-kinase and MAP kinase pathways. After phosphorylation, Nrf2 translocates to the nucleus, binds AREs and transactivates detoxifying enzymes and antioxidant enzymes, such as glutathione S-transferase, and superoxide dismutases and as a result cancer cells are able to mount antioxidative defense and have the ability to adapt oxidative stress. The pathway analysis has also demonstrated that at least seven signal transduction cascades were induced by ECM interaction with integrin heterodimers, which may trigger aberrant signaling which could lead to pancreatic cancer adenocarcinoma. The data have clearly shown the activation of INT-ILK-PT3K-ILKAP-AKT and Cav-GRB2-SOScRas- Raf-MEK cascades. Specially, the caveolin-1 seems to be important therapeutic target for the treatment of pancreatic cancer adenocarcinoma and could be used as prognostic biomarker.
Email: HSHUKLA@NDM.EDU