AbstractsBiology & Animal Science

Heat shock protein 72 expression in skeletal muscle samples from cachectic- and non-cachectic-pancreatic cancer patients

by Adriane Müller-Witt




Institution: Universität Ulm
Department: Medizinische Fakultät
Degree: PhD
Year: 2015
Record ID: 1113754
Full text PDF: http://vts.uni-ulm.de/docs/2015/9403/vts_9403_14155.pdf


Abstract

Cachexia is a clinical syndrome involving muscle loss, which often accompanies pancreatic cancer, though its causes are not fully understood. It is examined whether cachexia in pancreatic cancer patients is associated with increased expression of the stress protein heat shock protein 72 (Hsp 72) in skeletal muscle. It is also examined which clinical parameters of cachexia and pancreatic cancer (weight loss, C-reactive protein- and leucocyte-value, serum-albumin- and- protein-value and Carbohydrate Antigen 19-9) are associated with expression of skeletal muscle Hsp 72 and whether skeletal muscle Hsp 72 is associated with factors of cell survival (Insulin-like growth factor 1 (IGF-1), Myogenic Differentiation (MyoD), B-cell lymphoma 2 (Bcl-2)) or apoptosis (Bcl-2 associated X protein (Bax)). Parameters were measured by Western Blot and quantitative Real Time-PCR in skeletal muscle samples from 10 cachectic- and 11 non-cachectic-pancreatic cancer-, as well as 5 control-patients (no malign disease). Clinical data were obtained from patient charts. Due to the small number of patients statistical analysis was done in a descriptive orientating manner. There is a tendency towards higher expression of Hsp 72 protein in skeletal muscle samples from cachectic (20.61 ng) - compared to non-cachectic (15.65 ng) - cancer patients (p=0.133). Correlation analysis shows a negative association between pre-surgery serum-albumin value and skeletal muscle Hsp 72 protein content (Spearman’s correlation coefficient Rho -0.893) in cachectic patients. There is a positive association between Hsp 72 protein content and relative expression of Bcl-2 mRNA (Rho= 1.000) in skeletal muscle from non-cachectic cancer patients. The results indicate that metabolic stress causes increased expression of Hsp 72 protein in skeletal muscle of cachectic cancer patients and that Hsp 72 protein might protect skeletal muscle cells against wasting through a positive association with the anti-apoptotic factor Bcl-2.