Colonic Epithelial Cell Plasma Membranes. The colon is recognized as an important organ with regard to both normal physiological and pathological processes. Elucidation of its plasma membranes structure should greatly aid in further understanding these processes. In addition, cell surface changes in colonic epithelial cells assume added importance in view of the greater incidence of malignant transformation in this organ. We therefore propose to first isolate colonic epithelial cells from the heterogeneous population of cells found in this organ by methods already devised by the Principal Investigator. Crypt and surface epithelial cells from proximal and distal rat colon will also be separated. Lumenal and basolateral plasma membranes will then be isolated and purified. Each of these membranes biochemical composition including carbohydrate, protein, lipid, glycoprotein and glycolipid will be analyzed. In addition, each membranes """"""""fluidity"""""""" and protein and glycoprotein turnover and biosynthesis will be investigated during differentiation. After this is accomplished in the """"""""normal"""""""" rat colon, animals will be treated with the procarcinogen 1,2 Dimethylhydrazine with appropriate controls. Epithelial cells from tumors, """"""""transitional mucosa"""""""" and from """"""""normal"""""""" mucosa remote from tumors will then be separated and their plasma membranes isolated. These membranes will then have their biochemical composition (see above) analyzed. Tumor membranes will also be studied with regard to their protein and glycoprotein turnover and biosynthesis. It is anticipated that there should be differences between the normal and tumor, """"""""transitional mucosa"""""""" and """"""""normal"""""""" mucosa remote from the tumor membrane's composition which might be useful in detecting early or """"""""premalignant"""""""" changes. Compositional differences as well as differences in protein and glycoprotein turnover and biosynthesis between """"""""normal"""""""" and tumor membranes might also further aid in our understanding of the process of malignant transformation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036745-03
Application #
3174324
Study Section
(GCN)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Michael Reese Hosp & Medical Center (Chicago)
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60616
Mustafi, Reba; Dougherty, Urszula; Mustafi, Devkumar et al. (2017) ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer. Clin Cancer Res 23:549-561
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Ueno, Nobuhiro; Hasebe, Takumu; Kaneko, Atsushi et al. (2014) TU-100 (Daikenchuto) and ginger ameliorate anti-CD3 antibody induced T cell-mediated murine enteritis: microbe-independent effects involving Akt and NF-?B suppression. PLoS One 9:e97456
Dougherty, Urszula; Mustafi, Reba; Sadiq, Farhana et al. (2014) The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer. Clin Cancer Res 20:5848-5859
Wojdyla, Luke; Stone, Amanda L; Sethakorn, Nan et al. (2014) T-oligo as an anticancer agent in colorectal cancer. Biochem Biophys Res Commun 446:596-601
Mustafi, Reba; Dougherty, Urszula; Shah, Hardik et al. (2012) Both stromal cell and colonocyte epidermal growth factor receptors control HCT116 colon cancer cell growth in tumor xenografts. Carcinogenesis 33:1930-9
Chen, Peili; Kartha, Sreedharan; Bissonnette, Marc et al. (2012) AMP-18 facilitates assembly and stabilization of tight junctions to protect the colonic mucosal barrier. Inflamm Bowel Dis 18:1749-59

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