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Title: Neoplastic expression and cellular functions of proteolysis inducing factor/dermcidin
Author: Lowrie, A. G.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Proteolysis inducing factor (PIF) is a pro-cachectic glycopeptide purified from the urines of mice inoculated with the MAC16 tumour and from the urines of weight losing patients with pancreatic carcinoma. It arises from the dermcidin gene which produces 2 other peptides, Y-P30, an unglycosylated neuronal survival factor with homology to the PIF peptide core and DCD-1, an antibiotic peptide secreted by eccrine sweat glands which has no homology with PIF. We sought to investigate PIF / dermcidin expression in cell lines and pancreatic carcinoma tissue, the role of proteolysis inducing factor as a growth and survival factor in tumour cells and the influence on these effects of the structural features known to be important to the induction of cachexia by PIF and the functions of Y-P30 and dermcidin. Dermcidin was expressed by pancreatic carcinoma cell lines and primary human hepatocytes but not by the HuH7 cell line. In HuH7 cells induced expression promoted cell growth and improved survival following oxidative stress. The YP-30 / PIF core peptide sequence was sufficient to induce cell growth. Survival promotion did not require glycosylation but was prevented by mutagenesis of the asparagines residues of the PIF core peptide. Analysis of mRNA expression suggested dermidin was expressed in a low number of pancreatic carcinomas. Non-specific antibody binding prompted the development of mass spectrometry for detection of PIF in urine samples of patients with these tumours. This did not reveal PIF but did demonstrate other proteomic changes. We have demonstrated growth and survival functions of PIF / dermcidin which may be relevant in a range of physiological and pathological processes including cachexia and neoplasia. The PIF core peptide sequence appears to be important for these effects but its glycosylation does not appear to be required.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available