title: Reciprocal expression of CCAAT/enhancer binding proteins alpha and beta in hepatoblastomas and its prognostic significance.
abstract: Hepatoblastoma is one of the common pediatric solid tumors with frequent mutation of the beta-catenin gene which might be an early event of its carcinogenesis. However, the detailed molecular mechanism is still unknown. We studied the expression levels of CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta, which regulate differentiation and growth of embryonic hepatocytes, to establish whether or not they were involved in affecting the clinical behavior of hepatoblastoma. The quantitative real-time reverse transcriptase-PCR revealed that expression of C/EBPalpha mRNA was significantly up-regulated in tumors 223% (p=0.013) as compared with that in adjacent normal livers, while expression of C/EBPbeta was down-regulated to 27% (p=0.002). Of interest, the immunohistochemical analysis showed that expression of C/EBPalpha was higher and that of C/EBPbeta lower in the poorly differentiated tumor cells than in the well-differentiated cells within the same tumor. Furthermore, high expression of C/EBPalpha (p=0.047) as well as low expression of C/EBPbeta (p=0.025) was significantly associated with poor prognosis of the patients. Cox hazard model suggested that expression of C/EBPalpha and that of C/EBPbeta were independent indicators to predict the prognosis from age but not from histology. Thus, expression of C/EBP proteins may play an important role in the genesis and clinical behavior of hepatoblastoma probably by inducing different stages of arrest of differentiation.
authors.affiliation: Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tomizawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Horie
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sasaki
authors.forename: Kohei
authors.initials: K
authors.lastname: Hashizume
authors.forename: Eiso
authors.initials: E
authors.lastname: Hiyama
authors.forename: Michio
authors.initials: M
authors.lastname: Kaneko
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Suita
authors.forename: Hisami
authors.initials: H
authors.lastname: Ando
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Ohnuma
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis* / Q000502:physiology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis* / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018197:Hepatoblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta