title: Frequent alteration of the Yin Yang 1/Raf-1 kinase inhibitory protein ratio in hepatocellular carcinoma.
abstract: The transcription factor Yin Yang 1 (YY1) can favor several aspects of tumorigenesis. In turn, Raf-1 Kinase Inhibitor Protein (RKIP) inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist, and there are already separate evidences that relevant increases in YY1 and reductions in RKIP occur in hepatocellular carcinoma (HCC). However, the levels of the two factors have never been concomitantly examined in HCC. We evaluated by RT-PCR the mRNA levels of YY1, YY1AP, RKIP, and survivin in 35 clinical HCCs (91% HCV-related), in their adjacent cirrhotic tissues and in 6 healthy livers. Immunohistochemical analyses were also performed. The ratio of YY1 to RKIP mRNA was constantly profoundly inverted in the tumors compared with the adjacent nontumoral tissues. A similar result occurred frequently at protein level. Hyperactivation of YY1 in tumors was corroborated by its nuclear localization and the finding that in the tumors there were also increases in YY1AP, a YY1 coactivator not expressed in normal liver, and in survivin, as a possible target of YY1. The frequent alteration in the YY1-RKIP balance might represent a marker of malignant progression and be exploited for therapeutic interventions in HCC.
authors.affiliation: Dipartimento di Scienze Farmacologiche Pietro Benigno, Università degli Studi di Palermo, Palermo, Italy. mnotar@unipa.it
authors.forename: Monica
authors.initials: M
authors.lastname: Notarbartolo
authors.forename: Lydia
authors.initials: L
authors.lastname: Giannitrapani
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Vivona
authors.forename: Paola
authors.initials: P
authors.lastname: Poma
authors.forename: Manuela
authors.initials: M
authors.lastname: Labbozzetta
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Florena
authors.forename: Rossana
authors.initials: R
authors.lastname: Porcasi
authors.forename: Vito Michele Rosario
authors.initials: VM
authors.lastname: Muggeo
authors.forename: Luigi
authors.initials: L
authors.lastname: Sandonato
authors.forename: Melchiorre
authors.initials: M
authors.lastname: Cervello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montalto
authors.forename: Natale
authors.initials: N
authors.lastname: D'Alessandro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000077022:Survivin; D014157:Transcription Factors / Q000235:genetics; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D018797:Cell Cycle Proteins; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D049488:Phosphatidylethanolamine Binding Protein; D012333:RNA, Messenger; D000077022:Survivin; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C456659:YY1AP1 protein, human