Particularly, the heat shock proteins Hsp , Hsp , Hsp and Grp are differentially expressed in KCLR and KCLS cells. The heat shock protein complex, which exerts a protective position, interacts with Bcr Abl proteins and mediates their anti apoptotic results . In particular, Hsp is abundantly expressed in many cancer cells . Ectopic overexpression or induced endogenous levels of Hsp potently inhibit apoptosis . In acute leukemia cells, the over expression of Hsp enhances Bcr Abl expression therefore leading to anti apoptotic signaling and also to drug resistance . In addition, recent research indicate that Hsp over expression might be linked to drug resistance in K cells and that Hsp and Grp are below expressed in these cells . The identical authors observed that the anti apoptotic exercise of Bcr Abl may perhaps explain the expression of Hsp while in the K imatinib sensitive cells but not the in excess of expression detected from the resistant cells or in blast cells of imatinib resistant patients in whom Bcr Abl was not more than expressed. Moreover, a study addressing the results of imatinib on the protein expression profiles of Bcr Abl optimistic cells, demonstrated that, in K sensitive cells, Hsp was down regulated during the presence of imatinib .
In accordance with this particular observation, we observed that Hsp was down regulated in KCLR cells attributable to imatinib, and hence to Bcr Abl inhibition. This suggests that Hsp, as well as the other chaperon proteins identified in our GW9662 examine, could perform an indirect purpose in imatinib resistance and or the mechanisms of imatinib resistance in KCLR cells could also involve cellular pathways several from these of other resistant cell lines. Network also contains two SH containing, non receptor protein tyrosine phosphatases Shp and Shp . Reduction of SHP gene expression is observed in normal killer cell lymphomas as well as in other varieties of lymphoma and leukemia . Interestingly, decreased expression of Shp is related with progression of continual myeloid leukemia . In spite of scientific studies concentrating on the other tyrosine kinases possibly associated with imatinib resistance , little is acknowledged in regards to the role of tyrosine phosphatases in Ph cells and in sufferers who lack or eliminate the response to imatinib treatment .
Shp acts being a adverse regulator of cell proliferation . It will be normally regarded an antagonist of Orotic acid Shp that interacts together with the Bcr Abl core complex in K cells , and mediates Bcr Abl dependent neoplastic transformation . As a result, Shp down regulation is in line together with the continuous activation of Erk in KCLR cells and suggests that this protein could perform a function in imatinib resistance. Anxa also belongs to network and was observed by us to be downregulated in KCLR cells. Annexin A is usually a kDa member of your annexin household that structurally belongs to a family of ubiquitous phospholipids and calcium binding proteins.