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

reportActive / Technical Report | Accession Number: ADA453390 | Open PDF

Abstract:

The contract supports studies to define the role of the PIM1 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 STAT3 activation, expression of PIM1, and activation of NFkB signaling. Blockade of this pathway by expression of dominant negative PIM1proteins blocks drug-induced upregulation of NFkB activity, and sensitizes cells to docetaxel. Other studies specific aim 2 focus on identifying a mechanism through which PIM1 activates NFkB. We have unambiguously identified S937 as the major PIM1 phosphorylation site on the NFKB1p105 precursor protein, through use of LCMMSMS analysis. Interestingly PIM2 is only a weak kinase for this site. Additional data specific aim 3 have been generated to characterize a small molecule inhibitor of PIM1.

Author(s):
Lilly, Michael
Author Organization(s):
LOMA LINDA UNIV CA
Descriptive Note:
Annual rept. 1 Oct 2004-30 Sep 2005
Supplementary Note:
The original document contains color images. DOI: 10.21236/ADA453390
Pagination:
0019

Security Markings

DOCUMENT & CONTEXTUAL SUMMARY

Distribution:
Approved For Public Release
Distribution Statement:
Approved For Public Release; Distribution Is Unlimited. This Document Is Not Available From Dtic In Microfiche.

RECORD

Collection: TR
Identifying Numbers
Contract/Grant Number(s):
W81XWH-04-1-0887
Monitor Series:
USAMRMC
 Subject Terms
Joint Capability Areas:
JCA_1.2.3_Educating; JCA_7.2.1_Mitigate Lethal Effects; JCA_7.2_Mitigate; JCA_7_Protection; JCA_1.3.2_Personnel Management; JCA_5_Command and Control; JCA_5.3_Planning
Modernization Areas:
Autonomy
Communities of Interest:
No COI(s) Identified
Descriptor(s):
*MOLECULES, *CHEMOTHERAPY, *RESISTANCE(BIOLOGY), *PROSTATE CANCER, ACTIVATION, TARGETS, THERAPY, INHIBITORS, CELLS(BIOLOGY)
Field(s)/Group(s):
Biochemistry, Medicine and Medical Research
Keyword(s):
PIM1 KINASE CHEMOTHERAPY RESISTANCE PROSTATE CANCER, STAT3 ACTIVATION
Report Date:
2005 Oct 01
Creation Date:
2006 Sep 20