ABSTRACT
BACKGROUND: An overexpression of PIN1, the peptidyl-prolyl cis-trans isomerase, might cause cell cycle arrest and growth inhibition by binding to the p53 protein, a process leading to p53 stabilization. The rationale of this retrospective analysis was to evaluate the expression pattern of PIN1 in Merkel cell carcinomas (MCCs) and its suitability as a prognostic factor. METHODS: Samples of 27 MCCs were immunhistochemically stained for PIN1 expression and correlated with overall and disease-free survival of patients. RESULTS: All samples expressed PIN1. We showed a significantly better overall survival in patients with an overexpression of PIN1 than in patients with a weak PIN1 expression (p = .031), but expression was not significant for disease-free survival (p = .821). The 5-year overall survival rate was 14.4% in patients with weak and 50.9% in patients with overexpression of PIN1. CONCLUSIONS: PIN1 seems to be a prognostic factor for a better overall survival rate of patients with MCC.
Subject(s)
Carcinoma, Merkel Cell/enzymology , Carcinoma, Merkel Cell/mortality , Peptidylprolyl Isomerase/metabolism , Skin Neoplasms/enzymology , Skin Neoplasms/mortality , Aged , Aged, 80 and over , Carcinoma, Merkel Cell/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , NIMA-Interacting Peptidylprolyl Isomerase , Prognosis , Retrospective Studies , Skin Neoplasms/pathology , Survival AnalysisABSTRACT
BACKGROUND: 1Alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2) Vitamin D(3)] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin-CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)(2)Vitamin D(3), which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27). METHODS: Synchronized cells were treated with 1,25(OH)(2)Vitamin D(3) over 96 h. The cell cycle status and expression of cell cycle-regulating proteins was determined by fluorescence-activated cell sorting (FACS) and Western blotting. An overexpression of p18 in 1,25(OH)(2)Vitamin D(3) vs. ethanol-treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19. CONCLUSION: One mechanism by which 1,25(OH)(2)Vitamin D(3) controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)(2)Vitamin D(3) in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)(2)Vitamin D(3) in SCC25.
