Accession Number:

ADA465489

Title:

Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

Descriptive Note:

Annual rept., 1 Oct 2005-30 Sep 2006

Corporate Author:

LOMA LINDA UNIV CA

Personal Author(s):

Report Date:

2006-10-01

Pagination or Media Count:

29.0

Abstract:

The contract supports studies to define the role of the Pim-1 kinase in acquired resistance to chemotherapy by prostate cancer cells. Data to date for specific aim 1 define a signaling pathway induced by docetaxel, involving sequential steps of JAK12 activation, STAT3 phosphorylation, expression of Pim-1, and activation of NFkB signaling. Blockade of this pathway by expression of dominant negative Pim-1 proteins blocks drug-induced upregulation of NFkB activity, and sensitizes cells to docetaxel. Other studies specific aim 2 focus on identifying a mechanism through which Pim-1 activates NFkB. We have unambiguously identified S937 as the major Pim-1 phosphorylation site on the NFKB1p105 precursor protein, through use of LCMMSMS analysis. Other kinases that can phosphorylate this site include AKT and PKA. Additional data specific aim 3 have been published to describe a small molecule inhibitor of Pim-1. This molecule can sensitize prostate cancer cells to the cytotoxic effects of docetaxel in an additive or synergistic manner.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE