Pirin inhibits cellular senescence in melanocytic cells

Silvia Licciulli, Chiara Luise, Gaia Scafetta, Maria Capra, Giuseppina Giardina, Paolo Nuciforo, Silvano Bosari, Giuseppe Viale, Giovanni Mazzarol, Chiara Tonelli, Luisa Lanfrancone, Myriam Alcalay

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2397-2406
Number of pages10
JournalAmerican Journal of Pathology
Volume178
Issue number5
DOIs
Publication statusPublished - May 2011

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Pirin inhibits cellular senescence in melanocytic cells'. Together they form a unique fingerprint.

Cite this