Mortalin is over-expressed by colorectal adenocarcinomas and correlates with poor survival.
Using comparative proteomic analysis we have identified over-expression of mortalin in colorectal adenocarcinomas. Mortalin, also known as mitochondrial heat-shock protein 70 (mhsp 70), is involved in cell cycle regulation with important roles in cellular senescence and immortalization pathways. It is known to bind to and inactivate wild-type tumour suppressor protein p53 and influences the Ras-Raf-MAPK pathway. By immunostaining a colorectal cancer tissue microarray linked to a patient database, we further found that mortalin over-expression correlates with poor patient survival and, in multivariate analysis, is independent of standard prognostic variables (p = 0.04). Our findings demonstrate that mortalin over-expression may predict outcome in colorectal cancer and suggest that this protein is involved in colorectal neoplasia. Our experimental approach emphasises the analytical power of combining proteomics with tissue microarray analysis in the context of a well-defined tumour database.
Dundas
Sinclair R
SR
Department of Pathology, University of Aberdeen, Aberdeen, UK. s.r.dundas@abdn.ac.uk
Lawrie
Laura C
LC
Rooney
Patrick H
PH
Murray
Graeme I
GI
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D040901:Proteomics; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C080352:mortalin