Biomarkers & Clinical Research

Biography

Biography: Hem D Shukla

Abstract

Integrins are cell surface glycoproteins that are involved in cell-cell and cell-extracellular matrix (ECM) interactions. These interactions are the basis for a number of diverse effects that include cell migration and anchorage, cell growth and invasion. In the present investigation the proteomic analysis of oxidatively stressed BxPC3 human pancreatic cancer cells have shown the elevated level of both a6b4 integrin, caveolin-1, K-RAS, EGFR, annexin a4 and annexin a11 as compared to HPDE control. We have also identified the presence of a number of gene products involved in integrin signaling pathway and MAPK pathway. The bioinformatic analysis by Protein Center and Ingenuity Pathway Analysis have shown the altered integrin signaling pathway and MAPK pathway in Pancreatic Carcinoma Cell lines. Further, the activation of NRF2 transcriptional factor in BxPC-3 treated cells shows that It may bind to the DNA at the location of the Antioxidant Response Element (ARE) or also called 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 the 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 dismutase. 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 and lead to pancreatic cancer adenocarcinoma. The data have clearly shown the activation of INT-ILK-PT3K-ILKAP-AKT and Caveolin-GRB2-SOS-cRas-Raf-MEK cascade. These results may have some promise in therapeutic intervention in the treatment of pancreatic cancer adenocarcinoma.