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The mechanism by which retinol decre...

Dillard, Alice Clare.

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The mechanism by which retinol decreases beta-catenin protein in retinoic acid-resistant colon cancer cells.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The mechanism by which retinol decreases beta-catenin protein in retinoic acid-resistant colon cancer cells./
作者:	Dillard, Alice Clare.
面頁冊數:	143 p.
附註:	Adviser: Michelle Lane.
Contained By:	Dissertation Abstracts International68-06B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3271374
ISBN:	9780549104254

The mechanism by which retinol decreases beta-catenin protein in retinoic acid-resistant colon cancer cells.
Dillard, Alice Clare.

The mechanism by which retinol decreases beta-catenin protein in retinoic acid-resistant colon cancer cells. - 143 p.

Adviser: Michelle Lane.

Thesis (Ph.D.)--The University of Texas at Austin, 2007.

Cancer is the second leading cause of death in the United States, following cardiovascular disease. Colorectal cancer is the third leading cause of cancer death in the United States in both men and women. The American Cancer Society predicts over 153,000 new colorectal cancer cases and over 52,000 deaths due to colorectal cancer in 2007. Even though the mortality rate has continued to decrease for colorectal cancer in both men and women, there is only a 64% five-year survival rate, unless a distant metastasis is diagnosed, in which case the five-year survival rate drops to only 10%. All-trans retinoic acid (ATRA) is currently used as a chemotherapy for acute promyelocytic leukemia and some forms of skin cancer. Unfortunately, chemotherapy with ATRA often results in unpleasant side effects and ATRA-resistant tumors are common due to defects in ATRA signaling. The focus of this study is retinol's effects on beta-catenin, a protein essential for colon carcinogenesis. Our goal is to understand the mechanism by which retinol decreases the growth of ATRA-resistant human colon cancer cells. We first determined that retinol, not ATRA, decreases the growth of ATRA-resistant colon cancer cell lines by slowing cell cycle progression. Next, we examined the effects of retinol treatment on beta-catenin, a protein which regulates the transcription of cyclin D1 and c-myc, a protein essential for progress through the cell cycle. We found that retinol significantly decreased beta-catenin protein by inducing retinoid X receptor (RXR)alpha-mediated proteasomal degradation. Lastly, we showed that RXRalpha directs the degradation of beta-catenin by binding beta-catenin and transporting it to the proteasome for degradation. Based on these results, we propose a mechanism where retinol increases RXRalpha protein levels and RXRalpha-beta-catenin binding as well as the movement of beta-catenin to the cytosol where it is proteosomally degraded, ultimately leading to slowed cell cycle progression.

ISBN: 9780549104254Subjects--Topical Terms:

1017719
Biology, Molecular.

The mechanism by which retinol decreases beta-catenin protein in retinoic acid-resistant colon cancer cells.
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