The goal of this Project is the better understanding of the relationship of basal cell carcinomas (BCCs) to tissue stem cells, utilizing the Ptch1 mouse model of BCC carcinogenesis as a robust research tool of real relevance to human skin cancer and more broadly to skin biology and tumorigenesis. This application is a direct outgrowth of our own NIH-funded studies of BCC carcinogenesis in these mice as well as of the insights of others that have occurred during the past half-decade. Based on these results we propose herein a set of experiments designed to address two important questions - (i) What is the cell of origin of BCCs? This is a question which, to our knowledge, has not been answered directly and experimentally for any cancer for the carcinogeneic process in vivo (ii) Are the cells of a BCC heterogeneous in their capacity for self-renewal? We propose a set of ambitious studies which are of a scope commensurate with these questions, which we are confident are sufficiently powerful to answer the questions, and which are so inter-related that there is a real synergy in addressing all of them together. We are able to propose these studies because of our long-standing interest and expertise in BCC carcinogenesis and, especially, because new techniques and approaches just now for the first time make these studies possible.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA115992-04
Application #
7758208
Study Section
Special Emphasis Panel (ZRG1-MONC-U (01))
Program Officer
Watson, Joanna M
Project Start
2007-04-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
4
Fiscal Year
2010
Total Cost
$305,900
Indirect Cost
Name
Children's Hospital & Res Ctr at Oakland
Department
Type
DUNS #
076536184
City
Oakland
State
CA
Country
United States
Zip Code
94609
Epstein Jr, Ervin H (2011) Mommy - where do tumors come from? J Clin Invest 121:1681-3
Wang, Grace Ying; So, Po-Lin; Wang, Lynn et al. (2011) Establishment of murine basal cell carcinoma allografts: a potential model for preclinical drug testing and for molecular analysis. J Invest Dermatol 131:2298-305
Wang, Grace Ying; Wang, Joy; Mancianti, Maria-Laura et al. (2011) Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/-) mice. Cancer Cell 19:114-24
Epstein, Ervin H (2008) Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 8:743-54