Accession Number : ADA542494


Title :   Effects of Radiation on Proteasome Function in Prostate Cancer Cells


Descriptive Note : Annual summary 15 Jan 2010-14 Jan 2011


Corporate Author : CALIFORNIA UNIV LOS ANGELES


Personal Author(s) : Pajonk, Frank


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a542494.pdf


Report Date : Feb 2011


Pagination or Media Count : 13


Abstract : As cells progress through the various phases of the cell cycle the levels of most of the mammalian cyclins fluctuate dramatically. The major protease involved in the removal of cell cycle proteins is the fully regulated 26S proteasome, a multicatalytic protease responsible for the degradation of polyubiquitinated proteins (Glas et al. 1998). In vitro, inhibition of proteasome function prevents cell cycle progression and arrests cells at various stages of the cell cycle. Therefore, proteasome inhibitors like bortezomib (also known as PS-341 or Velcade) or Marizomib (also known as NPI-0052 or salinosporamide A) have been used to target cancer clinically (Kane et al. 2003). However, proteasome inhibitors alone failed to show significant anti-tumor activity and their combination with radiotherapy or established anticancer agents seems to be more promising. Many chemotherapeutic agents as well as radiation have differential efficacy against cancer cells in different phases of the cell cycle. Furthermore, certain chemotherapeutic drugs (Piccinini et al. 2001; Fekete et al. 2005) as well as ionizing radiation (Pajonk et al. 2001) affect proteasome function directly. Exact understanding of when and to which extent proteasome function is affected by a treatment modality is essential in order to better time the application of proteasome inhibitors in the clinic. Investigating the role of the proteasome in different prostate cancer cell subpopulations could be fundamental for the development of more specific and efficient therapies. In fact, both prostate cancer and benign prostatic hyperplasia are believed to arise as a result of changes in the balance between cell proliferation and differentiation (Isaacs et al. 1989; Bonkhoff et al. 1996). Experimental evidence suggests that the malignant transformation originates in a subset of primitive cells meanwhile most cells in an organ do not generate tumors (Huntly et al. 2004; Barker et al. 2009). In the previous year, we focused


Descriptors :   *DEGRADATION , *EFFICIENCY , *PROSTATE CANCER , *CYCLES , DRUGS , INHIBITION , CELLS(BIOLOGY) , IONIZING RADIATION , TRANSFORMATIONS , CHEMOTHERAPY , ORGANS(ANATOMY) , GROWTH(PHYSIOLOGY) , CHEMOTHERAPEUTIC AGENTS , RADIOTHERAPY , IN VITRO ANALYSIS , POPULATION , NEOPLASMS , ARRESTING(PROCESS) , PROTEINS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE