Maloney, Stephanie Louise (2010)
Ph.D. thesis, University of Birmingham.
Clusterin (CLU) is a multifunctional glycoprotein widely expressed as two isoforms. One isoform, sCLU is secreted, cytoplasmic and anti-apoptotic, the other, nCLU, is nuclear and pro-apoptotic. Seven genes, DKK3, TIMP1, CADM1, AKAP12, KLF4, RNASET2 and CLU were identified to be candidate tumour suppressor genes in cervical neoplasia and subsequent validation led to an evaluation of the regulation and expression of CLU at three sites of squamous cancer: the oral cavity, cervix and nasopharynx. Down-regulation of CLU was demonstrated in nasopharyngeal cancer (NPC) and oral cancer and loss of one CLU allele and methylation of the other in the NPC cell line C666-1. This defect has been repaired in this NPC cell line and showed that overexpression of the nuclear isoform of CLU resulted in reduced proliferation and decreased cell viability. Overexpression of both isoforms of CLU in C666-1 cells and their knockdown in HeLa cells regulates NF-kB activity, with a stabilisation of IkB\(\alpha\) following CLU overexpression in C666-1. Although sCLU is now considered a promising therapeutic target because of its anti-apoptotic function, with an antisense oligonucleotide currently undergoing clinical evaluation, results suggest that further consideration needs to be given to the possible tumour suppressor function of nCLU.
|Type of Work:||Ph.D. thesis.|
|School/Faculty:||Colleges (2008 onwards) > College of Medical & Dental Sciences|
|Department:||School of Cancer Sciences|
|Keywords:||Methylation, NF-kB, loss of heterozygosity, epigenetics|
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Institution:||University of Birmingham|
Repository Staff Only: item control page