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Current
Genomics
ISSN: 1389-2029
Current Genomics
Volume 8, Number 4, June 2007
Contents
Osmoadaptation of Mammalian Cells – An Orchestrated
Network of Protective Genes Pp. 209-218
C. Küper, F.-X. Beck and W. Neuhofer
[Abstract]
The Application of Single Nucleotide Polymorphism
Microarrays in Cancer Research Pp. 219-228
X. Mao, B.D. Young and Y.-J. Lu
[Abstract]
Enjoy the Silence: The Story of let-7 MicroRNA
and Cancer Pp. 229-233
J. Torrisani, L. Parmentier, L. Buscail and P. Cordelier
[Abstract]
Real-Time PCR: Revolutionizing Detection and
Expression Analysis of Genes Pp. 234-251
S.A. Deepak, K.R. Kottapalli, R. Rakwal, G. Oros, K.S.
Rangappa, H. Iwahashi, Y. Masuo and G.K. Agrawal
[Abstract]
The Role of Stress Proteins in Prostate Cancer
Pp. 252-261
A. So, B. Hadaschik, R. Sowery and M. Gleave
[Abstract]
Gene Expression Profiling and its Practice in Drug
Development Pp. 262-270
M.V. Chengalvala, V.M. Chennathukuzhi, D.S. Johnston,
P.E. Stevis and G.S. Kopf
[Abstract]
Abstracts
[Back to top]
Osmoadaptation of Mammalian Cells – An Orchestrated
Network of Protective Genes
C. Küper, F.-X. Beck and W. Neuhofer
In mammals, the cells of the renal medulla are physiologically
exposed to interstitial osmolalities several-fold higher that
found in any other tissue. Nevertheless, these cells not only
have the ability to survive in this harsh environment, but
also to function normally, which is critical for maintenance
of systemic electrolyte and fluid homeostasis. Over the last
two decades, a substantial body of evidence has accumulated,
indicating that sequential and well orchestrated genomic responses
are required to provide tolerance to osmotic stress. This
includes the enhanced expression and action of immediate-early
genes, growth arrest and DNA damage inducible genes (GADDs),
genes involved in cell cycle control and apoptosis, heat shock
proteins, and ultimately that of genes involved in the intracellular
accumulation of non-perturbing organic osmolytes. The present
review summarizes the sequence of genomic responses conferring
resistance against osmotic stress. In addition, the regulatory
mechanisms mediating the coordinated genomic response to osmotic
stress will be highlighted.
[Back to top]
The Application of Single Nucleotide Polymorphism
Microarrays in Cancer Research
X. Mao, B.D. Young and Y.-J. Lu
The development of microarray technology has had a significant
impact on the genetic analysis of human disease. The recently
developed single nucleotide polymorphism (SNP) array can be
used to measure both DNA polymorphism and dosage changes.
Our laboratory has applied SNP microarray analysis to uncover
frequent uniparental disomies and sub-microscopic genomic
copy number gains and losses in different cancers. This review
will focus on the wide range of applications of SNP microarray
analysis to cancer research. SNP array genotyping can determine
loss of heterozygosity, genomic copy number changes and DNA
methylation alterations of cancer cells. The same technology
can also be used to investigate allelic association in cancers.
Therefore, it can be applied to the identification of cancer
predisposition genes, oncogenes and tumor suppressor genes
in specific types of tumors. As a consequence, they have potential
in cancer risk assessment, diagnosis, prognosis and treatment
selection.
[Back to top]
Enjoy the Silence: The Story of let-7 MicroRNA
and Cancer
J. Torrisani, L. Parmentier, L. Buscail and P. Cordelier
Cancer is a multi-step disease involving dynamic changes
in the genome. However, studies on cancer genome so far have
focused most heavily on protein-coding genes, and our knowledge
on alterations of the functional noncoding sequences in cancer
is largely absent. MicroRNAs (miRNAs) are endogenous small
noncoding RNAs weighing 20 to 23 nucleotides that negatively
regulate gene expression at the posttranscriptional level
by base pairing to the 3' untranslated region of target messenger
RNAs. Hundreds of miRNAs have been identified in humans and
are evolutionarily conserved from plants to animals. These
tiny but potent molecules regulate various physiological and
pathological pathways such as cell differentiation and cell
proliferation. Recently, miRNA alterations have been linked
to the initiation and the progression of human cancer. As
a consequence, MiRNA-expression profiling of human tumors
has identified signatures associated with diagnosis, staging,
progression, prognosis and response to treatment. In addition,
profiling has been exploited to identify miRNA genes that
might represent downstream targets of activated oncogenic
pathways, or that target protein-coding genes involved in
cancer. Of importance, pioneering studies described let-7
miRNA as a negative regulator of the oncogenic family of Ras
guanosine triphosphatases in both Caenorhabditis elegans and
human tumor cell lines. Later, let-7 expression deregulation
was reported in several cancers, suggesting that let-7
may act as a tumor suppressor. This review will discuss the
late insights in let-7 function, the relationship
between let-7 and tumorigenesis, and the potential
for modulating let-7 expression for the treatment
of cancer.
[Back to top]
Real-Time PCR: Revolutionizing Detection and
Expression Analysis of Genes
S.A. Deepak, K.R. Kottapalli, R. Rakwal, G. Oros, K.S.
Rangappa, H. Iwahashi, Y. Masuo and G.K. Agrawal
Invention of polymerase chain reaction (PCR) technology by
Kary Mullis in 1984 gave birth to real-time PCR. Real-time
PCR — detection and expression analysis of gene(s) in
real-time — has revolutionized the 21st
century biological science due to its tremendous application
in quantitative genotyping, genetic variation of inter and
intra organisms, early diagnosis of disease, forensic, to
name a few. We comprehensively review various aspects of real-time
PCR, including technological refinement and application in
all scientific fields ranging from medical to environmental
issues, and to plant.
[Back to top]
The Role of Stress Proteins in Prostate Cancer
A. So, B. Hadaschik, R. Sowery and M. Gleave
The development of therapeutic resistance, after hormone or
chemotherapy for example, is the underlying basis for most
cancer deaths. Exposure to anticancer therapies induces expression
of many stress related proteins, including small heat shock
proteins (HSPs). HSPs interact with various client proteins
to assist in their folding and enhance the cellular recovery
from stress, thus restoring protein homeostasis and promoting
cell survival. The events of cell stress and cell death are
linked, as the induction of molecular chaperones appears to
function at key regulatory points in the control of apoptosis.
On the basis of these observations and on the role of molecular
chaperones in the regulation of steroid receptors, kinases,
caspases, and other protein remodelling events involved in
chromosome replication and changes in cell structure, it is
not surprising that molecular chaperones have been implicated
in the control of cell growth and in resistance to various
anticancer treatments that induce apoptosis. Recently, several
molecular chaperones such as Clusterin and HSP27 have been
reported to be involved in development and progression of
hormone-refractory prostate cancer. In this review, we address
some of the molecular and cellular events initiated by treatment
induced stress, and discuss the potential role of chaperone
proteins as targets for prostate cancer treatment.
[Back to top]
Gene Expression Profiling and its Practice in Drug
Development
M.V. Chengalvala, V.M. Chennathukuzhi, D.S. Johnston,
P.E. Stevis and G.S. Kopf
The availability of sequenced genomes of human and
many experimental animals necessitated the development of
new technologies and powerful computational tools that are
capable of exploiting these genomic data and ask intriguing
questions about complex nature of biological processes. This
gave impetus for developing whole genome approaches that can
produce functional information of genes in the form of expression
profiles and unscramble the relationships between variation
in gene expression and the resulting physiological outcome.
These profiles represent genetic fingerprints or catalogue
of genes that characterize the cell or tissue being studied
and provide a basis from which to begin an investigation of
the underlying biology. Among the most powerful and versatile
tools are high-density DNA microarrays to analyze the expression
patterns of large numbers of genes across different tissues
or within the same tissue under a variety of experimental
conditions or even between species. The wide spread use of
microarray technologies is generating large sets of data that
is stimulating the development of better analytical tools
so that functions can be predicted for novel genes. In this
review, the authors discuss how these profiles are being used
at various stages of the drug discovery process and help in
the identification of new drug targets, predict the function
of novel genes, and understand individual variability in response
to drugs.
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