Mark A. Nelson,
Associate Professor of Pathology and Arizona Cancer Center, Ph.D., Washington State University, 1989
mnelson@azcc.arizona.edu

Molecular mechanisms of  carcinogenesis, biochemical and molecular pharmacology of anti-cancer drugs.

Research Activities

My major field of interest is the molecular/cellular mechanisms involved in human tumorigenesis and cancer chemoprevention.  Modern recombinant DNA techniques including PCR, Flourescent in situ hybridization (FISH), comparative genomic hybridization (CGH), Northern blot, and Southern Blot are being utilized to study human melanoma.  For example, the increased cell number seen in neoplastic tissue can be viewed as a violation of normal homeostasis.  Either increased proliferation or decreased death might result in an expansion of cell numbers.  To date, most of our knowledge concerning oncogenic events has concentrated upon mechanisms of increased growth and proliferation.  Little is known about the control programmed cell death (i.e. apoptosis).  Recent evidence suggests that the failure of cells to undergo apoptotic cell death might be involved in the pathogenesis of a variety of human diseases including cancer.    Our cytogenetic studies in melanoma indicate that alterations of chromosome 1 are one of the  most frequent anomalies of melanoma and that chromosome break frequently cluster at band region 1p36.  The PITSLRE protein kinase gene locus maps to band region 1p36 and appears to be involved in apoptotic signaling.  Initial studies in our laboratory indicate alterations in PITSLRE gene copies and abnormal PITSLRE protein expression in melanoma. We are currently investigating the hypothesis that alterations in the PITSLRE gene locus on chromosome band 1p36 are involved in melanoma pathogenesis, possibly by disrupting apoptotic signaling pathways and preventing the elimination of tumor cells through normal checkpoint control.

I am also interested in the biochemical and molecular basis for the mechanism of action of selenium as an anticancer drug.  Selenium in the form of high selenium containing bakers yeast is being utilized as a intervention agent in cancer chemoprevention trials.  However, the mechanism of action is not well understood.  We have demonstrated that a defined componet of selenized yeast selenomethionine inhibits tumor cell growth, apoptosis, and cell cycle alterations in vitro. Although selenomethinonine appears to cause pertubation in polyamine metabolism in cells in culture, the anticancer effects of dietary selenium appear to independent of alterations in polyamine homeostasis.  More recent work in our laboratory demonstrates that cycloxygenase 2 (COX 2) protein expression and prostaglandin E2 levels are suppressed by selenium. This has led to the hypothesis that the anticancer effects of dietary selenium may mediated in part by inhibition of COX2 activity.  Current studies are directed at determine the molecular mechanism by selenium modulates COX2 as well as identifying COX-2 independent signal transduction pathways important for selenium.

Publications (Query PubMed for this investigator)

Chigbrow, M., Nelson, M.A.: Inhibition of mitotic cyclin B and cdc2 kinase activity by selenomethionine in synchronized colon cancer cells. Anti-Cancer Drugs 12:43-50, 2001.

Baines, A.T., Holubec, H., Basye, J.L., Thorne, P., Bhattacharyya, A.K., Spallholz, J., Shriver, B., Cui, H., Roe, D., Clark, L.C., Earnest, D.L., Nelson, M.A.: The effects of dietary selenomethionine on polyamines and azoxymethane-in aberrant crypts.  Cancer Letters 160(2):193-8, 2000.

Nelson, M.A., Radmacher, M.D., Simon, R., Aickin, M., Yang, J., Panda, L.  Emerson J., Roe, D., Adair, L., Thompson, F., Bangert, J., Leong, S.P., Taetle, R., Salomn, S., Trent, J.: Chromosome abnormalities in malignant melanoma: clinical significance of nonrandom chromosome abnormalities in 206 cases. Cancer  Genet Cytogenet 122(2):101-9, 2000.

Einspahr, J.G., Alberts, D.S., Warneke, J.A., Bozzo, P., Basye, J., Grogan, T.M., Nelson, M.A., Bowden, G.T.: Realtionship of p53 mutations to epidermal cell proliferation and apoptosos in human UV-induced skin carcinogenesis. Neoplasia 1(5):468-75, 1999.

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