Biomedical Summer Undergraduate Research Experience Program
(B-SURE)
The University of Texas Health Science Center at San Antonio (UTHSCSA)
CHATTERJEE,
Bandana (Molecular Medicine): Our laboratory
has been studying how the androgen receptor, which is a gene-regulatory
protein, functions to influence normal and aberrant cell growth and proliferation.
The androgen receptor normally resides in the cytoplasm as a functionally
inactive protein. The receptor is activated after it binds to its
partner hormone, known generically as “androgen”. The hormone-bound
androgen receptor (AR) is then translocated to the nucleus where it regulates
transcription of a whole array of genes that are known as androgen target
genes. The proteins encoded by the androgen target genes are involved
in a broad spectrum of normal physiological processes such as spermatogenesis,
male sexual development, skeletal growth, muscle mass development and brain
function. With chronic overexposure to androgen, target organs like
the prostate and testis become susceptible to uncontrolled cell growth
and proliferation, resulting in the development of tumor mass. Our
work focuses on the molecular mechanism that underlies altered target gene
expression in response to the androgen receptor (AR)/androgen signaling.
We are also asking the question how this signaling pathway contributes
to the development of prostate cancer.
We have identified
and characterized several androgen target genes whose transcription is
either positively or negatively influenced by AR signaling. We have
also completed an in-depth analysis of the AR gene itself and made the
observation that in several non-reproductive target tissues the expression
of AR is down regulated during the process of aging. Transcription factors
that coordinate this age-dependent down-regulation of AR includes Sp1,
NFkB and a yet to be cloned nuclear factor called
age-dependent factor (ADF). One current focus in our laboratory
is to clone the gene encoding the ADF protein and to characterize ADF activity.
In order to delineate the role of AR signaling in the development of prostate
cancer, we have developed a novel transgenic mouse model in which a dual-gene
approach allows highly amplified constitutive overproduction of AR in the
prostate. We have developed a second mouse model in which specific
tumor suppressing proteins like p53 is functionally inactivated in the
prostate in the background of AR overexpression. We are currently
investigating these mouse models for tumor development and for correlation
between the altered profile in androgen target gene expression and pathological
progression of prostate cancer.
Bandana
Chatterjee's Research Web Page.