MP7 Toxicogenomics in Environmental Studies
Monday, 14 November 2005: 8:00 AM - 5:30 PM in Exhibit Hall

(MUT-1117-825948) p53 family members from mussels: potential biomarkers for oncogenesis.

Muttray, A.¹, Cox, R.², St-Jean, S.³, Reinisch, C.², Baldwin, S.¹, ¹ Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, British Columbia, Canada² Laboratory of Aquatic Biomedicine, Marine Biological Laboratory, Woods Hole, Massachusetts, United States³ Environment Canada, National Water Research Institute, Burlington, Ontario, Canada

ABSTRACT- Our interest is in the development of DNA array technology for environmental effects monitoring amongst marine species. We have focused on characterization of potentially diagnostic genes, whose expression profiles may be linked to environmental contamination and/or disease onset. Here, we report on novel p53-like tumor suppressor genes in the bivalve molluscs Mytilus trossulus and edulis. These species, widely used for environmental assessment, develop a well-documented condition known as haemic neoplasia (leukemia). The role of p53 and its close relative p73 in onset of molluscan leukemia has been well documented. We previously isolated p53, and now report on two distinct and novel p73 isoforms from the gill of the mussels. The identification of a novel molluscan p73 of this type is particularly relevant to potential oncogenic transformations occurring during onset of leukemia. The nucleotide sequences of the two variants reported here are nearly identical with the exception that one contains a 360 nt truncation in the 5′ coding region. Based on this truncation and concomitant lack of a trans-activation (TA) domain, we designate this novel variant as a DeltaNp73 isoform. While the DeltaN isoform has been well characterized in mammalian species, this report is the first to identify this biologically important p73 isoform in any non-mammalian species. This research further illustrates the excellent utility of the molluscan model for studies involving the molecular mechanisms of oncogenesis in naturally occurring sessile populations. We are interested in the potential roles played by this novel DeltaNp73 isoform during oncogenic transformation in molluscan leukemia. In mammalian species, DeltaNp73 potently inhibits the tumor-suppressive function of p73 and p53, and its over-expression serves as a robust molecular marker for mammalian cancer. With the long-term goal of utilizing p73 gene expression as a molecular marker for oncogenic transformation in marine molluscs, our studies are currently underway to determine leukemia-specific p53, p73 and DeltaNp73 expression, as well as the potential inhibitory functions of the newly identified DeltaNp73 isoform.

Key words: p53 family, Mytilus, haemic neoplasia, toxicogenomics