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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
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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 |