Genetics of Prostate Cancer
the Macoska laboratory is focused on the elucidation of early genetic events
critical for malignant conversion in the prostate.
Two projects address this focus:
The first project involves the identification and biological
characterization of tumor suppressor genes mapping to the 8p chromosomal region.
This study is based upon previous work in our laboratory and others
showing that 8p sequence losses represent initiating or early promotional events
in prostate cancer. Our current
research on this project consists of constructing physical and transcriptional
maps of proximal 8p, then testing whether these genes meet criteria as candidate
tumor suppressors using complementation assays and mutational analysis.
We are also utilizing RNA profiling analysis to identify transcripts that
are absent or downregulated in cells deleted for all or part of 8p, and are
creating novel prostate epithelial cell lines to aid in this research.
2) The second project involves the
identification of genes that are differentially expressed in epithelium from
normal prostate and initiate primary prostate tumors. This project utilizes RNA profiling techniques, including
differential display and cDNA microarrays, to examine RNA isolated from cell
lines established from normal and malignant prostatic epithelium, or directly
from clinical samples. This project
has identified two groups of genes: those that are up-regulated (potentially
oncogenic) or down-regulated (potentially suppressive) during tumorigenesis in
the human prostate. In addition to
the elucidation of the transcriptional activation or repression of these genes
and their contribution to tumorigenesis, this research is also focused on the
development of DNA and protein markers useful towards the prediction of prostate
cancer progression and prognosis.
These projects are currently
supported by grants from the National Institutes of Health, the American Cancer
Society and the Department of Defense.
Macoska J.A., Trybus T.M., and Wojno K.J. 8p22 loss concurrent with 8c gain
is associated with poor outcome in prostate cancer. Urology
Macoska J.A., Beheshti B., Rhim J.S., Hukku
B., Lehr J., Pienta K.J., and Squire J.A. Genetic characterization of immortalized human prostate epithelial
cell cultures. Evidence for structural rearrangements of chromosome 8
and i(8q) chromosome formation in primary tumor-derived cells. Cancer Genetics and Cytogenetics
Schwab T.S., Stewart T., Lehr J., Pienta
K.J., Rhim J.S., and Macoska J.A.
Phenotypic characterization of immortalized normal and primary tumor-derived
human prostate epithelial cell cultures. Prostate 44(2):164-71, 2000.
Prasad, M.A., Wojno, K.J. and Macoska, J.A. Homozygous and Frequent
Deletion of Proximal 8p Sequences in Human Prostate Cancers:
Identification of a potential tumor suppressor gene site. Genes,
Chromosomes and Cancer 23: 255-262, 1998.