Protein kinase C [epsilon] promotes the survival of human prostate cancer cells / by Meagan McJilton.
| Author/creator | McJilton, Meagan author. |
| Other author | Terrian, David M., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 2002. |
| Description | xii, 98 leaves : illustrations (some color) ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Human prostate cancer (CaP) cells over-expressing protein kinase C epsilon (PKC[epsilon]) acquire a highly malignant phenotype that is androgen independent and autocrine in growth. Moreover, these CaP cells are highly tumorigenic in nude mice. These observations raise the question of whether CaP cells over-expressing PKC[epsilon] have also acquired the ability to survive in the presence of apoptotic signals, an important phenotypic characteristic of metastatic CaP cells. The LNCaP cell line provides an excellent model to study the effects of various known apoptotic stimuli, in particular the PKC agonist, phorbol-12-myristate-13-acetate (PMA). Several laboratories have independently shown that both PKC[alpha] and PKC[delta] are capable of inducing cell death through the intrinsic cell death pathway when LNCaP cells are exposed to PMA. Within 24 hours of PMA treatment more than 90% of the parental LNCaP cells undergo apoptosis, while LNCaP cells over-expressing PKC[epsilon] remain viable for at least 72 hours. Our studies demonstrate that signals transduced by PKC[epsilon] desensitize LNCaP cells to the pro-apoptotic effects of PMA by disrupting the intrinsic cell death pathway somewhere upstream of events leading to the release of cytochrome c from the intermembrane space of the mitochondria. In contrast, the expression of P PKC[epsilon] did not alter the apoptotic response of LNCaP cells to tumor necrosis factor-a (TNF-[alpha]), a potent activator of the extrinsic cell death pathway. Upstream of the mitochondrion, PKC is known to suppress pro-apoptotic activity of the BH3-only protein. Bad, by promoting the heterodimerization of Bad with the cytosolic protein 14-3-3[zeta]. However, our data show that the levels of this heterodimer are not altered hy the over-expression of PKC[epsilon] in LNCaP cells, indicating that such a mechanism is unlikely to be involved. Another such upstream of the mitochondria event that may be occurring to cause resistance to PMA-induced apoptosis of these LNCaP cells over-expressing PKC[epsilon] is Bax being sequestered in the cytosol. PKC[epsilon] may promote CaP cell survival through a direct or indirect interaction with Bax, another pro-apoptotic member of the Bcl-2 family that is directly responsibly for the opening of the recently discovered mitochondrial apoptosis-induced channel (MAC). Because these studies were based on the forced expression of PKC[epsilon], the CWR-R1 cell line was used to examine PKC[epsilon]'s endogenous role in PMA-induced apoptosis. It does appear that endogenous PKC[epsilon] in required to protect CaP cells from PMA-induced apoptosis. |
| General note | Presented to the faculty of the Department of Biology. |
| General note | Advisor: David M. Terrian |
| Dissertation note | M.S. East Carolina University 2002 |
| Bibliography note | Includes bibliographical references ([91]-98). |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |
Availability
| Library | Location | Call Number | Status | Item Actions |
|---|---|---|---|---|
| Joyner | University Archives | ASK AT SPECIAL COLLECTIONS DESK | ✔ Available | Request Material |
| Electronic Resources | Access Content Online | ✔ Available |