Accession Number : ADA613551


Title :   Therapeutic Value of PLK1 Knockdown in Combination with Prostate Cancer Drugs in PIM-1 Overexpressing Prostate Cancer Cells


Descriptive Note : Final rept. 15 Apr 2010-14 Aug 2014


Corporate Author : NORTHWESTERN UNIV CHICAGO IL


Personal Author(s) : Roh, Meejeon


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a613551.pdf


Report Date : 13 Nov 2014


Pagination or Media Count : 38


Abstract : The goal of this project is to test whether depletion of PLK1 will result in synthetic lethality in Pim-1 overexpressing cells and whether depletion of PLK1 will further sensitize Pim-1 overexpressing cells to prostate cancer drugs. Pim-1 is highly overexpressed in prostate cancer and overexpression of Pim-1 leads to genomic instability in prostate epithelial cells. PIM1 synergizes with c-MYC to induce advanced prostate cancer. Using a siRNA library screen, we identified Polo-like kinase (PLK1) as a promising target whose knockdown can specifically reduce the cell viability of Pim-1 overexpressing cells. PLK1 is also overexpressed in a wide variety of cancer types including prostate and its expression frequently correlates with poor patient prognosis. In this study, we found that PLK1 inhibition is particularly effective against PIM1-overexpressing prostate tumors, possibly due to interaction between PIM1 and PLK1. Furthermore, PIM1 and PLK1 are frequently co-expressed in human prostate tumors. These data suggest that targeting PLK1 could be exploited for therapeutic purposes specifically in prostate cancer patients with PIM1 overexpression.


Descriptors :   *DRUGS , *PHOSPHORUS TRANSFERASES , *PROSTATE CANCER , CELLS(BIOLOGY) , LETHALITY , NEOPLASMS


Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE