Date of Award

2006

Degree Name

Biomedical Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Maiyon Park

Second Advisor

Simon Collier

Third Advisor

Gho-Zhang Zhu

Abstract

In the present study, we investigated the involvement of Chmp1 (Chromatin ModifyingProtein 1/Charged Multivesicular body Protein 1) in the development of mousepancreatic acinar tumor cell line. CRL 2151 cell line was transfected with Chmp1/CS2vector to compare growth, morphology and expression of Chmp1, p53 and pp53 (ser37) with control-transfected cells. CRL 2151 cells were treated with all-trans retinoicacid (ATRA) to compare growth, morphology and expression of Chmp1 and p53 withcontrol-treated cells. Strabismus was used as control. Results showed inhibition ofgrowth but no morphological change in transfected cells. Western blot analysis showedthat Chmp1 transfection upregulated the expression of p53, pp53 and Stbm temporarily.Treatment of cells with ATRA did not inhibit growth or show morphological change.However, Western blot analysis demonstrated the upregulation of Chmp1, p53 andStbm proteins. Microarray analysis of samples transfected with Chmp1 or treated withretinoic acid was done to determine if the same set of genes will be regulated. The proapoptoticgenes Bad and Bak are among the genes up-regulated. Cell division cycleprotein, Cdca7, was among the genes down-regulated. Results from Western blotanalysis confirmed the expression of Bad and Bak genes. Taken together, these resultssuggest that Chmp1 functions in the suppression of pancreatic tumor by the retinoicacid signaling pathway.

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