Welcome to the Lab of Dr. Chris Mueller in Department of Pathology at Queen's University
Page Last Updated: 2009 September 15
Email: muellerc (at) queensu (dot) ca
Office Phone: 613-533-6751
Transcription Factors Growth and Differentiation Cancer
We are examining the role that regulation of the expression of the
BRCA1 tumor suppressor gene plays in the risk and development of
sporadic breast cancer. The inherited form of breast cancer is known
to result from genetic defects in the BRCA1 and 2 genes. However, between
them they only account for some 10% of all cases. The development of
the sporadic form of breast cancer is correlated with the decreased expression
of the BRCA1 gene. We are studying the molecular mechanisms which regulate
this process and how mutations in the genes which control BRCA1
expression may be responsible for the initiation and progression
of breast cancer. We are also studying how changes in BRCA1 expression
may contribute to the risk of developing breast cancer. We have found
that stress related hormones reduce BRCA1 expression, and this decrease
in tumor suppressor activity may create an opportunity for transformation
to occur. Similarly, we are examining whether the protective effect of
pregnancy may result from increased BRCA1 expression.
We are also investigating molecular mechanisms which regulate growth,
differentiation and immortalization in all types of cells. The Sp1/3
family of transcription factors is known to be involved in the
regulation of genes such as the cyclin dependent kinase inhibitor
p21Cip1/Waf1 and telomerase reverse transcriptase. Changes in the
DNA binding activity, stability, post-translational modification
and sub-nuclear localization of these proteins play an important
role in regulating diverse cellular processes. This work has
application in understanding all types of cells and how normal
processes are disrupted to give rise to cancer.
Mueller, C.R. and Roskelley, C.D. (2002). Transcriptional regulation of the BRCA1 gene and its relationship to sporadic breast cancer. Breast Cancer Research. 5(1):45-52 .
Atlas, E., Stramwasser, M., Mueller, CR. (2001) A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element. Oncogene. 20(48): 7110-4114.
Atlas, E., Stramwasser M., Whiskin, K. and Mueller, C.R. (2000) GA-binding protein alpha/beta is a critical regulator of the BRCA1 promoter. Oncogene (19): 1933-1940
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Queen's University Department of Pathology and Molecular Medicine