Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression

Pirin inhibits cellular senescence in melanocytic cells / S. Licciulli, C. Luise, G. Scafetta, M. Capra, G. Giardina, P. Nuciforo, S. Bosari, G. Viale, G. Mazzarol, C. Tonelli, L. Lanfrancone, M. Alcalay. - In: THE AMERICAN JOURNAL OF PATHOLOGY. - ISSN 0002-9440. - 178:5(2011 May), pp. 2397-2406.

Pirin inhibits cellular senescence in melanocytic cells

G. Scafetta;M. Capra;S. Bosari;G. Viale;C. Tonelli;M. Alcalay
Ultimo
2011

Abstract

Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression
carrier proteins ; humans ; melanocytes ; skin neoplasms ; reverse transcriptase polymerase chain reaction ; melanoma ; blotting western ; tissue array analysis ; nuclear proteins ; cell aging ; nevus pigmented ; adult ; middle aged ; immunohistochemistry ; cell transformation neoplastic
Settore MED/08 - Anatomia Patologica
Settore MED/04 - Patologia Generale
mag-2011
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/167565
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