title: Prion protein expression and the M129V polymorphism of the PRNP gene in patients with colorectal cancer.
abstract: The prion protein, PrP(C), is known mostly for its involvement in neurodegenerative spongiform encephalopathies. However, a role for this molecule in cancer is becoming increasingly recognized partly because it promotes cell proliferation and inhibits apoptosis. Moreover, the codon 129 polymorphism (M129V) of the PRNP gene (the PrP(C)-encoding gene) has been associated with neurodegenerative disease development and severity, while no information is available regarding its role in colorectal cancer (CRC) incidence and disease progression. We have previously reported that expression levels of PRNP may have a prognostic value in CRC, suggesting a role for the prion protein in CRC. The aim of this study was to investigate retrospectively the possible role of M129V and PrP(C) expression in patients with CRC. The M129V single nucleotide polymorphism was genotyped by real time polymerase chain reactions in 110 patients with CRC and 124 healthy donors. Moreover, protein expression was assessed by immunohistochemistry in 68 patients with CRC. Allele frequencies were similar in patients and healthy controls indicating that the M129V polymorphism is not a risk factor for CRC. Furthermore, it did not correlate with any clinicopathological parameters. By contrast, PrP(C) expression was highly elevated in neoplastic compared to normal tissue and differed depending on the primary site. Interestingly, protein levels were correlated with disease recurrence (P = 0.007). Conclusively, PrP(C) overexpression may constitute a prognostic marker for disease recurrence and potentially a new target for anticancer therapy. However, further studies are needed to evaluate prospectively the role of PrP(C) expression in patients with CRC.
authors.affiliation: Clinical Oncology Laboratory, Medical School, University of Patras, Rion, Greece.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Antonacopoulou
authors.forename: Maria
authors.initials: M
authors.lastname: Palli
authors.forename: Stella
authors.initials: S
authors.lastname: Marousi
authors.forename: Fotinos-Ioannis
authors.initials: FI
authors.lastname: Dimitrakopoulos
authors.forename: Urania
authors.initials: U
authors.lastname: Kyriakopoulou
authors.forename: Athanasios C
authors.initials: AC
authors.lastname: Tsamandas
authors.forename: Chrisoula D
authors.initials: CD
authors.lastname: Scopa
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018621:PrPC Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D018621:PrPC Proteins; D012333:RNA, Messenger