The major objective of this research project is to investigate the molecular mechanism whereby the putative tumor suppressor gene deleted-in oral cancer-1 (doc-1) suppresses transformation phenotypes of malignant oral keratinocytes. Data will be presented to support the hypothesis that doc-1 exerts its effect on cancer cells by regulating their progression through the cell cycle in a manner that results in a significant increase in the accumulation of cells in the S phase. Detailed studies will be conducted to elucidate the role of doc-1 in the cell cycle. This application encompasses four specific aims: (1) to determine the pattern of expression of doc-1 in human tissues; 92) to determine the role of phosphorylation in the regulation of Doc-1 protein function; (3) to examine the role of doc-1 in the cell cycle; and (4) to identify the functional partners of Doc-1. The proposed studies will be conducted by a team of investigators active in the field of cell cycle and cancer research Close collaborations with the investigators conducting the other two research projects as well as with the Cell Culture and Tissue Bank and Pathology Cores will ensure that these two studies are validated at the clinical level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program Projects (P01)
Project #
1P01DE012467-01A1
Application #
6270378
Study Section
Project Start
1998-04-01
Project End
1999-03-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Crissey, Mary Ann S; Guo, Rong-Jun; Funakoshi, Shinsuke et al. (2011) Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development. Gastroenterology 140:517-528.e8
Guo, Rong-Jun; Funakoshi, Shinsuke; Lee, Hannah H et al. (2010) The intestine-specific transcription factor Cdx2 inhibits beta-catenin/TCF transcriptional activity by disrupting the beta-catenin-TCF protein complex. Carcinogenesis 31:159-66
Funakoshi, Shinsuke; Kong, Jianping; Crissey, Mary Ann et al. (2010) Intestine-specific transcription factor Cdx2 induces E-cadherin function by enhancing the trafficking of E-cadherin to the cell membrane. Am J Physiol Gastrointest Liver Physiol 299:G1054-67
Kalabis, Jiri; Oyama, Kenji; Okawa, Takaomi et al. (2008) A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. J Clin Invest 118:3860-9
Oyama, K; Okawa, T; Nakagawa, H et al. (2007) AKT induces senescence in primary esophageal epithelial cells but is permissive for differentiation as revealed in organotypic culture. Oncogene 26:2353-64
Maley, Carlo C; Rustgi, Anil K (2006) Barrett's esophagus and its progression to adenocarcinoma. J Natl Compr Canc Netw 4:367-74
Natarajan, Easwar; Omobono 2nd, John D; Guo, Zongyou et al. (2006) A keratinocyte hypermotility/growth-arrest response involving laminin 5 and p16INK4A activated in wound healing and senescence. Am J Pathol 168:1821-37
Cao, Wenhui; Cavacini, Lisa A; Tillman, Karl C et al. (2005) CD40 function in squamous cell cancer of the head and neck. Oral Oncol 41:462-9
Ishii, Hideshi; Vecchione, Andrea; Furukawa, Yusuke et al. (2004) Differentially expressed genes execute zinc-induced apoptosis in precancerous esophageal epithelium of zinc-deficient rats. Oncogene 23:8040-8
Buajeeb, Waranun; Zhang, Xue; Ohyama, Hiroe et al. (2004) Interaction of the CDK2-associated protein-1, p12(DOC-1/CDK2AP1), with its homolog, p14(DOC-1R). Biochem Biophys Res Commun 315:998-1003

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