BACKGROUND: Loss of TGF-beta growth control is considered as a hallmark of several human neoplasms including melanoma. Resistance of cancer cells to TGF-beta has been linked to mutations in proteins involved in the TGF-beta pathway. In melanoma such mutations have not been observed. C-Ski and SnoN, two structurally and functionally highly homologous proteins, are known as negative regulators in the TGF-beta signaling pathway. C-Ski and SnoN expression levels and subcellular localization have been associated with clinicopathological parameters and tumour progression in several human malignancies. In melanoma cell lines, high c-Ski and SnoN expression levels have been described. OBJECTIVE: The objective of this study was to evaluate the clinical value of c-Ski and SnoN expression in primary cutaneous melanoma. METHODS: We evaluated c-Ski and SnoN expression by immunohistochemical staining in 120 primary melanomas. Possible associations between c-Ski and SnoN staining patterns and clinicopathological parameters were analyzed. RESULTS: Nuclear c-Ski expression was significantly associated with thicker and ulcerated tumours. The percentage of SnoN positivity was higher in ulcerated tumours and in the sentinel node positive group. CONCLUSION: These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression.
BACKGROUND: Loss of TGF-beta growth control is considered as a hallmark of several humanneoplasms including melanoma. Resistance of cancer cells to TGF-beta has been linked to mutations in proteins involved in the TGF-beta pathway. In melanoma such mutations have not been observed. C-Ski and SnoN, two structurally and functionally highly homologous proteins, are known as negative regulators in the TGF-beta signaling pathway. C-Ski and SnoN expression levels and subcellular localization have been associated with clinicopathological parameters and tumour progression in several humanmalignancies. In melanoma cell lines, high c-Ski and SnoN expression levels have been described. OBJECTIVE: The objective of this study was to evaluate the clinical value of c-Ski and SnoN expression in primary cutaneous melanoma. METHODS: We evaluated c-Ski and SnoN expression by immunohistochemical staining in 120 primary melanomas. Possible associations between c-Ski and SnoN staining patterns and clinicopathological parameters were analyzed. RESULTS: Nuclear c-Ski expression was significantly associated with thicker and ulcerated tumours. The percentage of SnoN positivity was higher in ulcerated tumours and in the sentinel node positive group. CONCLUSION: These results suggest that c-Ski and SnoN, mediators in TGF-beta resistance, might be implicated in melanoma growth and progression.
Authors: Dahu Chen; Qiushi Lin; Neil Box; Dennis Roop; Shunsuke Ishii; Koichi Matsuzaki; Tao Fan; Thomas J Hornyak; Jon A Reed; Ed Stavnezer; Nikolai A Timchenko; Estela E Medrano Journal: Pigment Cell Melanoma Res Date: 2009-12 Impact factor: 4.693
Authors: Delphine Javelaud; Leon van Kempen; Vasileia I Alexaki; Erwan Le Scolan; Kunxin Luo; Alain Mauviel Journal: Mol Cancer Date: 2011-01-06 Impact factor: 27.401
Authors: Angeles C Tecalco-Cruz; Diana G Ríos-López; Genaro Vázquez-Victorio; Reyna E Rosales-Alvarez; Marina Macías-Silva Journal: Signal Transduct Target Ther Date: 2018-06-08