title: Pirin inhibits cellular senescence in melanocytic cells.
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.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology (Istituto Europeo di Oncologia), Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Licciulli
authors.forename: Chiara
authors.initials: C
authors.lastname: Luise
authors.forename: Gaia
authors.initials: G
authors.lastname: Scafetta
authors.forename: Maria
authors.initials: M
authors.lastname: Capra
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Giardina
authors.forename: Paolo
authors.initials: P
authors.lastname: Nuciforo
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mazzarol
authors.forename: Chiara
authors.initials: C
authors.lastname: Tonelli
authors.forename: Luisa
authors.initials: L
authors.lastname: Lanfrancone
authors.forename: Myriam
authors.initials: M
authors.lastname: Alcalay
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology*; D049308:Dioxygenases; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; D049308:Dioxygenases; C105340:PIR protein, human