Scott M. Dehm, Ph.D. Assistant Professor Department of Laboratory Medicine & Pathology University of Saskatchewan, 2003, Ph.D. dehm@umn.edu 612-625-1504 office 612-625-1520 lab

Research Interests:

Androgen receptor activation in prostate cancer

Our laboratory investigates the role of the androgen receptor (AR) in prostate cancer development and progression. The AR is a steroid hormone receptor transcription factor of central importance in normal and cancerous prostate tissue. Due to this so-called androgen-dependence, the mainstay treatment for relapsed or metastatic prostate cancer is androgen depletion. The primary limitation of androgen depletion is that prostate cancer eventually develops resistance and recurs with a lethal androgen depletion-independent phenotype. Clinical and experimental evidence supports the current paradigm that androgen deletion-independent prostate cancer remains dependent on AR activity for ongoing growth and survival. We employ molecular, biochemical, cell biology, and genetic approaches to understand the mechanisms of AR transcriptional de-regulation in cell- and xenograft-based models of prostate cancer progression. We have identified alternative mechanisms of AR activation that are impervious to current modes of androgen depletion, and are studying whether these mechanisms of AR activation can be exploited to develop novel targeted therapies for advanced prostate cancer.

Selected Recent Publications:

• Raclaw KA, Heemers HV, Kidd EM, Dehm SM, Tindall DJ. 2008. Induction of FLIP expression by androgens protects prostate cancer cells from TRAIL-mediated apoptosis. The Prostate, 68: 1696-706.
• Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. 2008. Splicing of a novel AR exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res., 68: 5469-77.
• Heemers HV, Regan KM, Dehm SM, Tindall DJ. 2007. Androgen induction of the androgen receptor co-activator FHL2: evidence for a role for serum response factor in prostate cancer. Cancer Res., 67 :10592-9.
• Dehm SM, Regan KM, Schmidt, LJ, Tindall DJ. 2007. Selective role of an NH2-terminal WxxLF motif for aberrant androgen receptor activation in androgen depletion-independent prostate cancer cells. Cancer Res. 67: 10067-77.
• Dehm SM, Tindall DJ. 2007. Androgen Receptor Structural and Functional Elements: Role and Regulation in Prostate Cancer. Mol. Endocrinology. 2: 2855-63.
• Dehm SM, Tindall DJ. 2006. Ligand-independent androgen receptor activity is activation function-2-independent and resistant to antiandrogens in androgen refractory prostate cancer cells.J. Biol. Chem. 28:27882-93.
• Dehm SM, Tindall DJ. 2006. Molecular regulation of androgen action in prostate cancer. J. Cell Biochem. 99:333-44.
• Debes JD, Comuzzi B, Schmidt LJ, Dehm SM, Culig Z, Tindall DJ. 2005. p300 regulates androgen receptor-independent expression of prostate-specific antigen in prostate cancer cells treated chronically with interleukin-6. Cancer Res. 65, 5965-73.
• Dehm SM, Tindall DJ. 2005. Regulation of androgen receptor signaling in prostate cancer. Expert Rev. Anticancer Ther. 5: 63-74.
  
  

Last modified on: February 25, 2009