title: KIF20A mRNA and its product MKlp2 are increased during hepatocyte proliferation and hepatocarcinogenesis.
abstract: Mitotic kinesin-like protein 2 (MKlp2), a microtubule-associated motor, is required during mitosis exit for the final step of cytokinesis. It also contributes to retrograde vesicular trafficking from the Golgi apparatus to the endoplasmic reticulum in interphase. The KIF20A gene encoding MKlp2 is controlled by the E2F-retinoblastoma protein-p16 pathway, and its widely expressed mRNA is found in fetal and proliferating adult tissues. The expression pattern and function of MKlp2 in the adult liver, however, have not been investigated. We report herein that MKlp2 transiently accumulates in vivo during mouse liver regeneration after partial hepatectomy and is strongly overexpressed in preneoplastic and neoplastic mouse liver. In vitro in mitogen-stimulated primary hepatocytes, MKlp2 accumulated in the nucleus during the G2 phase of the cell cycle coincident with the mitotic kinase Aurora B. Human hepatoma cell lines exhibited high levels of MKlp2; however, it was undetectable in normal human hepatocytes. RNAi-mediated MKlp2 knockdown in hepatoma cells induced polyploidization consistent with its essential function in promoting cytokinesis and inhibited cell proliferation without inducing apoptosis. KIF20A mRNA was strongly accumulated in a large series of human hepatocellular carcinomas, with the highest expression observed in tumors with genomic instability. Accumulation of MKlp2 in normal proliferating, preneoplastic, and transformed hepatocytes suggests that MKlp2 contributes to both normal and pathologic hepatocyte proliferation and is linked to tumor aggressiveness in human hepatocellular carcinomas.
authors: Université Pierre et Marie Curie (UPMC), Paris, France.
authors: Isabelle
authors: I
authors: Gasnereau
authors: Mathieu
authors: M
authors: Boissan
authors: Germain
authors: G
authors: Margall-Ducos
authors: Gabrielle
authors: G
authors: Couchy
authors: Dominique
authors: D
authors: Wendum
authors: Florence
authors: F
authors: Bourgain-Guglielmetti
authors: Chantal
authors: C
authors: Desdouets
authors: Marie-Lise
authors: ML
authors: Lacombe
authors: Jessica
authors: J
authors: Zucman-Rossi
authors: Joëlle
authors: J
authors: Sobczak-Thépot
mesh_terms: D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005260:Female; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: C410089:KIF20A protein, human; D019394:Ki-67 Antigen; D008934:Mitogens; D016547:Kinesins