title: GLI1 is involved in cell cycle regulation and proliferation of NT2 embryonal carcinoma stem cells.
abstract: Hedgehog (HH) signaling plays a critical role during embryogenesis and regulates early development of multiple tissues and organs, including the central nervous system. Although much has been revealed of the diverse functions of the HH signaling pathway, it is still unclear how the effects of altered HH signaling are interpreted by specific cell types. We have investigated the role of the HH transcription factor glioma-associated oncogene homolog 1 (GLI1) in the human Ntera2/D1 (NT2) embryonal carcinoma stem cell line. The study revealed that expression of GLI1 and its direct transcriptional target Patched (PTCH) is downregulated in the early stages of retinoic acid-induced neuronal differentiation of NT2 cells. To identify transcriptional targets of the HH transcription factor GLI1 in NT2 cells, we performed global expression profiling following GLI1 RNA interference (RNAi). Of the 8500 transcripts represented on the microarrays, expression of 88 genes was downregulated and expression of 26 genes was upregulated. Nineteen of these genes are involved in cell cycle and proliferation. Further, GLI1 RNAi leads to a significant decrease in NT2 proliferation and changes expression of G1 phase cyclins. In conclusion, our results suggest that GLI1 is involved in cell cycle and proliferation control in the embryonal carcinoma stem cell line NT2.
authors.affiliation: Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Janni
authors.initials: J
authors.lastname: Vestergaard
authors.forename: Allan
authors.initials: A
authors.lastname: Lind-Thomsen
authors.forename: Mikkel W
authors.initials: MW
authors.lastname: Pedersen
authors.forename: Hanne Ostergaard
authors.initials: HO
authors.lastname: Jarmer
authors.forename: Mads
authors.initials: M
authors.lastname: Bak
authors.forename: Lis
authors.initials: L
authors.lastname: Hasholt
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.forename: Lars Allan
authors.initials: LA
authors.lastname: Larsen
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D054278:Embryonal Carcinoma Stem Cells / Q000378:metabolism* / Q000473:pathology; D016193:G1 Phase / Q000502:physiology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014212:Tretinoin / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D014212:Tretinoin