| dc.contributor.author | Dunfield, Lesley Deanne. | en_US |
| dc.date.accessioned | 2014-10-21T12:38:46Z | |
| dc.date.available | 2003 | |
| dc.date.issued | 2003 | en_US |
| dc.identifier.other | AAINQ83712 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/55937 | |
| dc.description | Ovarian cancer is the most lethal of the gynecologic: cancers. The majority of ovarian cancers arise from the ovarian surface epithelium (OSE). Transforming growth factor beta (TGFbeta) inhibits proliferation of the OSE, which secretes and expresses receptors for TGFbeta. Resistance to the anti-proliferative effect of TGFbeta is demonstrated in numerous cancers, due to defects in the TGFbeta signaling pathway. TGFbeta signals through a receptor complex, which activates intracellular signaling molecules known as Smads. Activated Smads translocate to the nucleus, interact with other transcription factors, and modulate target gene expression. | en_US |
| dc.description | This study investigated the TGFbeta signaling pathway in primary human ovarian cancer cells. All components of the TGFbeta signaling pathway are expressed and functional in primary ovarian cancer cells. Furthermore, primary ovarian cancer cells respond to the anti-proliferative effect of TGFbeta, which is partly mediated by TGFbeta-induced up-regulation of p15 INK4B. Although primary ovarian cancer cells respond to the anti-proliferative effect of TGFbeta in cell culture, ovarian cancer cells in vivo are exposed to TGFbeta but continue to proliferate. Therefore, mechanisms must exist to inhibit the anti-proliferative effect of TGFbeta contributing to uncontrolled cellular proliferation in vivo. | en_US |
| dc.description | Numerous signaling pathways can converge with the TGFbeta signaling pathway to modulate its effects. Epidermal growth factor (EGF) is mitogenic to ovarian cancer cells, and can modulate TGFbeta signaling. This study demonstrates that EGF inhibits the anti-proliferative effect of TGFbeta in primary ovarian cancer cells. TGFbeta-induced up-regulation of p15 INK4B is decreased by EGF, which likely accounts for the EGF inhibition of the anti-proliferative effect of TGFbeta. Therefore, although the TGFbeta signaling pathway remains functional in primary ovarian cancer cells, inhibition of the anti-proliferative effect of TGFbeta by factors such as EGF may occur in vivo. Inhibition of these factors may reverse resistance to TGFbeta and may be a potential therapy for ovarian cancer patients. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2003. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Health Sciences, Pharmacology. | en_US |
| dc.title | The role of transforming growth factor beta signaling in human ovarian cancer cells. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
