Colorectal cancer is the 4th most widespread cause of cancer mortality. One of the pathways that are involved in the development of colorectal cancer is the arachidonic acid metabolizing lipoxygenase (LOX) pathway. Inflammatory molecules formed from this pathway exert profound effects that may exacerbate the development and progression of colon and other cancers. 15 lipoxygenase-1 (15-LOX-1) is a member of LOX protein family that metabolizes primarily linoleic acid to 13-(S)-HODE. Several lines of evidence support an antiangiogenic role for 15-LOX-1, especially through 13-(S)-HODE. The expression of 15-LOX-1 is lost in colon cancer cells. Our aim in this thesis was to study whether 15-LOX-1 expression has an anticarcinogenic role, particularly on the metastatic and angiogenic potential of colon cancer cells. For this purpose, 15-LOX-1 was introduced into HCT-116 colon cancer cell lines. Having confirmed 15-LOX-1 expression and activity it was observed that expression of 15-LOX-1 significantly decreased cell proliferation, cell motility, anchorage-independent growth, migration and invasion across Matrigel, the expression of the metastasis-related MTA-1 protein, neoangiogenesis and induced apoptosis. Mechanistically, most of these effects were arbitrated by the 15-LOX-1
mediated inhibition of the inflammatory transcription factor NF-&kappa / B via the orphan nuclear receptor PPAR&gamma / . In conclusion, we propose that 15-LOX-1 has anti-tumorigenic properties and can be exploited for therapeutic benefits.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12615333/index.pdf |
| Date | 01 December 2012 |
| Creators | Cimen, Ismail |
| Contributors | Sreeparna, Banerjee |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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