title: A potential role for the homeoprotein Hhex in hepatocellular carcinoma progression.
abstract: Hepatocellular carcinoma (HCC), the most common primary malignant tumor of the liver, often associated with the dysregulation of transcriptional pathways involved in cell growth and differentiation. The hematopoietically expressed homeobox protein (Hhex) is an important transcription factor throughout liver development and is essential to liver bud formation and hepatoblast differentiation. Here, we report a relationship between Hhex expression and HCC. First, adenovirus-mediated Hhex delivery into the hepatoma cell line, Hepa1-6, resulted in decreased expression of several proto-oncogenes (c-Jun and Bcl2), increased expression of some tumor suppressor genes (P53 and Rb), and enhanced expression of a cluster of hepatocytic and bile ductular markers. Second, Hhex expression significantly attenuated Hepa1-6 tumorigenicity in nude mice. Third, we report a correlation between Hhex expression and the differentiation state of human HCC. In 24 cases of clinical specimens, there was a significant difference in Hhex expression between poorly differentiated HCC and well-differentiated HCC (P < 0.001). Taken together, these results indicate that Hhex is a potential candidate molecular marker for HCC pathological evaluation, suggesting a need to evaluate Hhex as a potential target for therapeutic intervention.
authors.affiliation: Department of Cell Biology, Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Pu
authors.initials: P
authors.lastname: You
authors.forename: Jun-Peng
authors.initials: JP
authors.lastname: Zhao
authors.forename: Shou-Long
authors.initials: SL
authors.lastname: Zhang
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Song
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Fu
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Ye
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Zi
authors.forename: Dong-Fu
authors.initials: DF
authors.lastname: Xie
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhu
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
chemical_list: C078492:HHEX protein, human; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors