It is proposed to use a newly derived mouse epidermal clone 291, selected both for high efficiency and maintenance of terminal differentiation response to Ca++ in an assay designed to more precisely quantitate chemical carcinogen effects in terminally differentiating epithelial cells, Alteration of the response to calcium is quantitated by counts of colonies which proliferate in 1.4 mM Ca++ relative to differentiation and sloughing of normal colonies inder these conditions. Using the clonal density Ca++ shift assay, transformation frequencies have been calculated relative to clonogenic cells plated. During the coming year, the reproducibility of modifications in the assay is being verified using 4 carcinogens which are active in mouse epidermis, and 2 in active structural analogs. The effect of 3 retinoid derivatives in transformation frequency and malignent potential in vivo is being quantitated. The normal and carcinogen altered mouse epidermal clones are being examined for Ca++ dependent changes in potein synthesis in an effort to define molecular markers of normal """"""""differentiation"""""""" and of transformation on these cells. Such markers are of particular importance, since reliable markers of transformation in lining epithelial cell have not yet been defined. Analysis of possible markers is being performed by polyacrylamide gel electrophoresis of metabolically labell proteins, obtained from transformed vs non transformed subclones of line 291 which have been incubated in culture medium containing a range of Ca++ concentrations. In collaborative efforts monoclonal and polyclonal antibody to keratins and spectrin are being used to assess whether these proteins respond to Ca++ in the subclones. Long term objectives are to use the clonal density epidermal transformation assay to evaluate mechanisms of action of initiating and promoting agents in chemical carcinogenesis, and of """"""""anti tumor"""""""" and differentiation modulating drugs in the inhibition of carcinogenesis.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Chemical Pathology Study Section (CPA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Roswell Park Cancer Institute Corp
United States
Zip Code
Liu, Y; Kulesz-Martin, M F (2006) Sliding into home: facilitated p53 search for targets by the basic DNA binding domain. Cell Death Differ 13:881-4
Horn, Elizabeth J; Albor, Amador; Liu, Yuangang et al. (2004) RING protein Trim32 associated with skin carcinogenesis has anti-apoptotic and E3-ubiquitin ligase properties. Carcinogenesis 25:157-67
Liu, Yuangang; Lagowski, James P; Vanderbeek, Gretchen E et al. (2004) Facilitated search for specific genomic targets by p53 C-terminal basic DNA binding domain. Cancer Biol Ther 3:1102-8
McAllister, Shane C; Hansen, Scott G; Ruhl, Rebecca A et al. (2004) Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. Blood 103:3465-73
Knights, Chad D; Liu, Yuangang; Appella, Ettore et al. (2003) Defective p53 post-translational modification required for wild type p53 inactivation in malignant epithelial cells with mdm2 gene amplification. J Biol Chem 278:52890-900
Wang, Zhiping; Liu, Yuangang; Mori, Motomi et al. (2002) Gene expression profiling of initiated epidermal cells with benign or malignant tumor fates. Carcinogenesis 23:635-43
Huang, Hua; Kaku, Shinsuke; Knights, Chad et al. (2002) Repression of transcription and interference with DNA binding of TATA-binding protein by C-terminal alternatively spliced p53. Exp Cell Res 279:248-59
Liu, Y; Asch, H; Kulesz-Martin, M F (2001) Functional quantification of DNA-binding proteins p53 and estrogen receptor in cells and tumor tissues by DNA affinity immunoblotting. Cancer Res 61:5402-6
Liu, Y; Kulesz-Martin, M (2001) p53 protein at the hub of cellular DNA damage response pathways through sequence-specific and non-sequence-specific DNA binding. Carcinogenesis 22:851-60
Davis, T L; Rabinovitz, I; Futscher, B W et al. (2001) Identification of a novel structural variant of the alpha 6 integrin. J Biol Chem 276:26099-106

Showing the most recent 10 out of 28 publications