Ovarian cancer is regarded as the most lethal gynecological malignancy around the
world. Despite the advancing medical improvements in both surgery and
chemotherapy, the mortality rate did not appear to be reduced. This could be
account for the late diagnosis of ovarian cancer until advanced stage. Recently, p-21
activated kinase 4 (PAK4), as a potential significant prognostic marker of ovarian
cancer, has been widely studied on its contribution in oncogenesis properties. It was
suggested that PAK4 proteins were activated and confer chemoresistance in ovarian
cancers.
In this study, we hypothesized that the up-regulation of PAK4 in ovarian cancers
maybe resulted from mutations and amplification in genomic DNA level.
Investigations on PAK4 genetic alterations were carried out. Recurrent mutations
were found in the kinase domain of PAK4 in three ovarian cancer cell lines and two
clinical samples. Single mutation was found in the exon 3 of PAK4 coding for
GTPase binding domain (GTB). Amplifications of PAK4 genomic DNA were also
found in four ovarian cancer cell lines.
On top of that, dysregulated PAK4 level in chemosensitivity ovarian cancer cell line,
A2780s showed PAK4 contribution in protection against apoptosis. Meanwhile
PAK4 transfected chemoresistance cell line A2780cp also showed similar effect to
PAK4 transfected A2780s. Kinase-dead and constitutively active PAK4 did not
show any significance contribution to the apoptosis property. This may suggest that
PAK4 do not operate all kinase domains towards apoptotic function. Immortalized
normal ovarian epithelial cell line, HOSE6-3 was also upregulated with PAK4
transfection. However it did not induce the oncogenesis property of cell survival. / published_or_final_version / Pathology / Master / Master of Medical Sciences
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/173867 |
| Date | January 2012 |
| Creators | Chu, Chun-ho, Terence., 朱雋皞. |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B48273995 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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