Studies

Cancer Biology Group

CD34:

The hematopoietic cell surface marker CD34 is uniquely expressed in epidermal cells (keratinocytes) located in the bulge region of the murine hair follicle, which is widely regarded to contain a population of epidermal stem and progenitor cells. Use of the cell surface localization of this protein enabled the group to enrich for living keratinocytes specifically derived from the mouse hair follicle bulge region, which were subsequently shown to be slowly cycling with a high proliferative potential—properties associated with stem and progenitor cells. The group is currently interested in characterizing gene expression responses specific to CD34-positive stem and progenitor cells following chemical exposure, in order to elucidate very early genetic events that may contribute to neoplastic development. Insight into proliferative and gene expression responses using this model has potential utility in understanding the mechanisms of skin cancer development in humans, and can provide potential gene targets for clinical intervention and prevention strategies.

Localization of the hematopoietic stem cell marker CD34 in the bulge region of mouse hair follicles is coincident with tritiated thymidine-label retaining cells, which is an in vivo method of labeling slowly cycling stem and progenitor cells.

ABCA13:

The group continues its investigation into the transgene insertional mutation of ABCA13 that blocks expression of the gene product. This insertional mutation alters serum lipids and disrupts the normal accretion of polyunsaturated fatty acids (PUFA) in numerous tissues in the animal. Ongoing work of Dr. Cannon continues to focus on the precise regions that determine cellular localization and protein interactive domains in hopes of providing therapeutic targets for drug design. The brain specifically seems to be most disturbed by this insertional event, resulting in a severe deficiency of omega 3 polyunsaturated fatty acids (PUFA). These PUFA acids have been strongly associated with mental disorders, including depression, epilepsy, and schizophrenia.

Dss1:

The primary goal of this study was to identify and characterize novel genes involved in early skin neoplastic development induced by TPA, using an in vivo mouse model system (v-Ha-ras, TgAC line). Dss1 (deleted in split hand/split foot 1) has been identified as a novel TPA-inducible gene expressed in mouse epidermis, with possible involvement in early skin tumorigenesis. Future studies will focus on phosphorylation of Dss1 in terms of clinical relevance, and the potential role of Dss1 in proteasome assembly will be investigated. The specific targets of phospho-Dss1 have not yet been identified, and this will be an important step in defining the molecular basis for the downstream effects of Dss1.

p19ARF:

Recent evidence suggests the p19ARF tumor suppressor gene is a critical sensor that limits the malignant potential of oncogene-initiated cells. The group is exploring the functional interaction of oncogenic H-ras and p19ARF in vivo through the use of transgenic mouse models. This work has identified a strong functional interaction between these genes in several specific tumors. These tumor models are currently being characterized, with the hope they can provide important insight into mechanisms driving their development.

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