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Cancer Biology Group

Skin Tumor Development

Raymond W. Tennant, Ph.D.
Raymond W. Tennant, Ph.D.(
Principal Investigator

Tel (919) 541-4141
Fax (919) 541-1460
P.O. Box 12233
Mail Drop F1-05
Research Triangle Park, North Carolina 27709
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Research Summary

Molecular characterization of wound healing and tumor development in mice.
Molecular characterization of wound healing and tumor development in mice using global gene expression analysis reveals patterns that differentiate between the two processes, highlighting potential gene targets for intervention and prevention in the neoplastic process.
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The Cancer Biology Group focuses on early events in skin tumor development as a means to understand the earliest cellular origin of skin cancers and genetic events that underlie early neoplastic transformation. Conventional therapies have until recently depended on treatment of late stages of tumor growth and non-specific mechanisms of cellular injury. By focusing on understanding early events in tumor induction, the group hopes to gain insights into targets for intervention that more specifically inhibit tumor growth.

Recent study results have identified CD34 as a marker of keratinoctye progenitor (stem) cells, and studies are in progress to assess the role of CD34+ cells in tumor development. The group has also used the CD34+ marker to isolate and analyze the functional phenotype of these cells using microarray and informatic methods. The goal is to identify a functional phenotype of the skin stem cells compared to CD34+ hematopoietic stem cells. Recent studies have identified other genes that play an important role in cellular susceptibility to ras tumor induction. These genes include: 1) ABCA13, a novel transporter mutated through the insertion of the ras transgene in the Tg.AC mouse model; 2) Dss1, a novel 70 amino acid protein which when phosphorylated plays an important role in ras-induced transformation of keratinocytes, and 3) p19/Arf, which has been found to play a critical role in tumor induction. In addition, crosses between TgAC and p19/Arf transgenic mice result in a novel tumor phenotype that has many characteristics of human gastrointestinal stromal (GIST) tumors.

Major areas of research:

  • Identification and characterization of the cellular origin of tumors using the mouse model of two-stage carcinogenesis
  • Identification and characterization of critical genes which are involved in ras-mediated tumor induction and progression
  • Characterization of interactions between genes and signaling pathways that mediate oncogenic progression

Current projects:

  • Role of epidermal stem cells in skin cancer development
  • Role of Dss1 in proteasome assembly and function
  • Interaction between oncogenic ras and p19Arf in GIST pathogenesis
  • Involvement of ABCA13 in ras transgene induction (Tg.AC model) and mental disorders

Raymond W. Tennant, Ph.D., heads the Cancer Biology Group within the Laboratory of Molecular Toxicology. He received his Ph.D. from the Department of Microbiology at the University of Notre Dame in 1963. He has published over 150 peer-reviewed articles in leading biomedical journals, as well as several book chapters. He served as scientist at Oak Ridge National Laboratory from 1966-1980 before joining NIEHS in 1980. Most recently, he served as the Director of the National Center for Toxicogenomics at NIEHS from 2000-2006.

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Last Reviewed: July 19, 2007