The PIM-3 kinase was the PIM family member most often associated with PC oncogenesis and was also the kinase inhibited the most by Ter among more than 600 kinases investigated.
These results suggest combining drug therapies that inhibit Pim kinases, such as Pim-3, with chemotherapeutic agents, to aid in decreasing chemoresistance in pancreatic cancer.
We constructed retroviral vectors for human Pim-3 and a kinase-dead mutant of human Pim-3 (K69M); the retroviral supernatants generated from these vectors were then used to infect the human pancreatic cancer cell line MiaPaCa-2 to establish stable cell lines.
The growth inhibitory effects of T26 were reversed by overexpression of Pim-3 cDNA in human pancreatic cancer cells, indicating that T26 acts primarily on Pim-3.
Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines.