U of M
Section of
Urology

RESEARCH

Recent Publications from the Macoska Laboratory  

Molecular Genetics of Prostate Cancer

            Research in the Macoska laboratory is focused on the elucidation of early genetic events critical for malignant conversion in the prostate.  Two projects address this focus:

          1)  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 55(5):776-82, 2000.

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 120(1):50-7, 2000.

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.