Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRaf(V600E) mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments. We found that deletion of Sox2 specifically in Pten null and BRafV600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wt mice. In addition, tumor growth was similar between Sox2 wt and Sox2 deleted (del) melanomas. By querying publicly available databases, we did not find statistically significant differences in SOX2 expression levels between benign nevi and melanomas, and analysis on two melanoma patient cohorts confirmed that Sox2 levels did not significantly change between primary and metastatic melanomas. Melanoma cell lines derived from both Sox2 genotypes showed a similar sensitivity to vemurafenib treatment and the same ability to develop vemurafenib resistance in long-term cultures. Development of vemurafenib resistance was not dependent on SOX2 expression also in human melanoma cell lines in vitro. Our findings exclude an oncogenic function for Sox2 during melanoma development and do not support a role for this transcription factor in the acquisition of resistance to BRAFi treatments.Oncogene advance online publication, 3 April 2017; doi:10.1038/onc.2017.53.

Cesarini, V., Guida, E., Todaro, F., Di Agostino, S., Tassinari, V., Nicolis, S., et al. (2017). Sox2 is not required for melanomagenesis, melanoma growth and melanoma metastasis in vivo. ONCOGENE, 36(31), 4508-4515 [10.1038/onc.2017.53].

Sox2 is not required for melanomagenesis, melanoma growth and melanoma metastasis in vivo

CESARINI, VALERIANA;Guida, E;TODARO, FEDERICA;TASSINARI, VALENTINA;Botti, E;ROSSI, PELLEGRINO;DOLCI IANNINI, SUSANNA
2017-01-01

Abstract

Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRaf(V600E) mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments. We found that deletion of Sox2 specifically in Pten null and BRafV600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wt mice. In addition, tumor growth was similar between Sox2 wt and Sox2 deleted (del) melanomas. By querying publicly available databases, we did not find statistically significant differences in SOX2 expression levels between benign nevi and melanomas, and analysis on two melanoma patient cohorts confirmed that Sox2 levels did not significantly change between primary and metastatic melanomas. Melanoma cell lines derived from both Sox2 genotypes showed a similar sensitivity to vemurafenib treatment and the same ability to develop vemurafenib resistance in long-term cultures. Development of vemurafenib resistance was not dependent on SOX2 expression also in human melanoma cell lines in vitro. Our findings exclude an oncogenic function for Sox2 during melanoma development and do not support a role for this transcription factor in the acquisition of resistance to BRAFi treatments.Oncogene advance online publication, 3 April 2017; doi:10.1038/onc.2017.53.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/16
English
SOX2, MELANOMA, BRAFV600E, PTEN, VEMURAFENIB, CONDITIONAL GENE MODIFICATION
http://www.nature.com/onc/journal/vaop/ncurrent/full/onc201753a.html
Cesarini, V., Guida, E., Todaro, F., Di Agostino, S., Tassinari, V., Nicolis, S., et al. (2017). Sox2 is not required for melanomagenesis, melanoma growth and melanoma metastasis in vivo. ONCOGENE, 36(31), 4508-4515 [10.1038/onc.2017.53].
Cesarini, V; Guida, E; Todaro, F; Di Agostino, S; Tassinari, V; Nicolis, S; Favaro, R; Caporali, S; Lacal, P; Botti, E; Costanzo, A; Rossi, P; Jannini, E; DOLCI IANNINI, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/179289
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