A reversible transgenic mouse model for skin cancer will be used to investigate the relationship between neoplasia and anaplasia, with the long term goal of better understanding the consequences of oncogene activation and inactivation for differentiation.
The specific aims are 1) to test the hypothesis that neoplastic INV-MycERTM keratinocytes will differentiate upon removal of ectopic Myc function; 2) to identify the in vivo alterations in keratinocyte gene expression upon activation and subsequent deactivation of c-MycERTM; 3) to engineer a ubiquitously prospective, conditionally expressed, regulatable c-Myc transgenic mouse. IHC and ISH will be employed to assess the differentiation state of INV-MycERTM keratinocytes in SA1 while tissue microdissection coupled with high throughput microarray analysis will define the transcriptional basis for Myc-induced change in SA2. For SA3, the MycERTM transgene, linked by way of an IRES to EGFP and preceded by a floxed Stop cassette, will be targeted to a ubiquitously active locus by homologous recombination.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA099363-01
Application #
6585101
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2003-06-11
Project End
2006-06-10
Budget Start
2003-06-11
Budget End
2004-06-10
Support Year
1
Fiscal Year
2003
Total Cost
$48,148
Indirect Cost
Name
University of California San Francisco
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Murphy, Daniel J; Junttila, Melissa R; Pouyet, Laurent et al. (2008) Distinct thresholds govern Myc's biological output in vivo. Cancer Cell 14:447-57
Murphy, Daniel J; Swigart, Lamorna Brown; Israel, Mark A et al. (2004) Id2 is dispensable for Myc-induced epidermal neoplasia. Mol Cell Biol 24:2083-90