Elucidating The Functional Roles Of Peroxisome Proliferator Activated Receptor Beta Delta In Human Colon Cancer Cells
Download and Read Elucidating The Functional Roles Of Peroxisome Proliferator Activated Receptor Beta Delta In Human Colon Cancer Cells full books in PDF, ePUB, and Kindle. Read online free Elucidating The Functional Roles Of Peroxisome Proliferator Activated Receptor Beta Delta In Human Colon Cancer Cells ebook anywhere anytime directly on your device. We cannot guarantee that every ebooks is available!
ELUCIDATING THE FUNCTIONAL ROLES OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR [beta]/[delta] IN HUMAN COLON CANCER CELLS.
Author | : Xiaohan Wang |
Publisher | : |
Total Pages | : |
Release | : 2019 |
Genre | : |
ISBN | : |
Download ELUCIDATING THE FUNCTIONAL ROLES OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR [beta]/[delta] IN HUMAN COLON CANCER CELLS. Book in PDF, Epub and Kindle
Peroxisome proliferator-activated receptor / (PPAR/) is an important regulator in various physiological processes, including lipid metabolism and glucose homeostasis. However, its role in cancer remains controversial. Although PPAR/ is highly expressed in the intestines of normal adults, it has been reported to be up- or down-regulated during colon tumorigenesis. Researchers have not reached a consensus for whether PPAR/ is beneficial, detrimental, or unrelated to colon cancer initiation, survival, growth, and metastasis, in mouse or and human cancer models.One of the first mechanisms described that PPAR/ promotes carcinogenesis was the hypothesis that PPAR/ is a target gene of the oncogenic APC/-CATENIN pathway, a major pathway that is activated by mutations in colon cancer. However, subsequent studies did not observe a correlation between PPAR/ expression and -CATENIN activation, and questioned whether PPARD (gene coding for PPAR/) is a bona fide APC/-CATENIN target protein. Moreover, the functionality of PPAR/ as influenced by the APC/-CATENIN pathway, has not been critically examined to date. Therefore, in the first part of this thesis, the hypothesis that PPAR/ is functionally regulated by the APC/-CATENIN pathway as a tumor-promoting protein was tested. We first investigated whether mutations of the APC/CTNNB1 (-CATENIN) genes or overexpression of functional -CATENIN modulate PPAR/ cellular retention and its response to ligand activation in human colon cancer cell lines. We further examined the effect of ligand activation of PPAR/ using a classic agonist, as well as selective repression of PPAR/ using ligands that stimulate its transcriptional repression activity, on the growth of colon cancer cells with wild-type or mutant APC/CTNNB1. We observed that cytosol and nuclear retention of PPAR/, with or without ligand activation, were not different between cell lines with wild-type or mutant APC/CTNNB1 (gene coding for -CATENIN). Second, target gene activation of PPAR/ following ligand activation occurred faster in cell lines with mutant APC/CTNNB1 compared to a non-mutant cell line, although this difference was not observed with transient overexpression of -CATENIN. Third, ligand activation and selective repression of PPAR/ inhibited growth in several APC/CTNNB1 mutant cell lines but had no effect on the non-mutant cell line. These results suggest that cellular retention and transcriptional activity of PPAR/ are not directly regulated by the APC/-CATENIN pathway. However, the results also suggest that PPAR/ may be enhanced by the presence of APC/CTNNB1 mutations in human colon cancer cell lines.The role of PPAR/ in colon cancer invasion and metastasis also remains elusive. In the second part of this thesis, the influence of PPAR/ activation on malignancy-related features of colon cancer was examined. We hypothesized that ligand activation or selective repression of PPAR/ would inhibit anchorage-independent growth, migration, invasion, epithelial to mesenchymal transition (EMT), and metalloprotease (MMP) activity. Results, some preliminary in nature, showed that selective repression of PPAR/ reduced anchorage-independent growth by inducing apoptosis, inhibited migration, and reduced EMT marker expression, but did not change TNF/TGF-induced MMP activity. By contrast, ligand activation of PPAR/ reduced migration and TNF/TGF-induced MMP activity, but did not affect anchorage-independent growth and EMT marker expression. These results suggest that both ligand activation and selective repression of PPAR/ reduce the malignant potential of colon cancer, although the underlying mechanisms could be different. Combined, results from this study indicate that PPAR/ is not functionally regulated by the APC/-CATENIN pathway. Further, ligand activation or selective repression of PPAR/ using synthetic ligands may modulate colon cancer growth and malignancy-related features, in particular in cells with APC/CTNNB1 mutations.
ELUCIDATING THE FUNCTIONAL ROLES OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR [beta]/[delta] IN HUMAN COLON CANCER CELLS. Related Books
Pages:
Pages:
Pages: 1872
Pages: 322
Pages: 875