Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer cell line OVCAR3.
Recent evidence suggested an involvement of homeobox genes in tumorigenesis. Here we investigated whether one of homeobox-containing genes, Msx1, might be involved in the regulation of cell proliferation and cell cycle using Msx1 overexpressing human ovarian cancer cell line, OVCAR3. Overexpression of Msx1 in OVCAR3 cells inhibited cell proliferation by markedly increasing the length of the G1 phase of the cell cycle over control cells. Consistent with this result, dramatic suppression of cyclins D1, D3, E, cyclin-dependent kinase 4, c-Jun, and Rb was observed. Elevated expression of genes involved in the growth arrest and apoptosis (GADD153 and apoptotic cystein protease MCH4) and suppression of proliferation associated protein gene (PAG) in Msx1-overexpressing cells by cDNA expression array analysis provide further evidence for a potential repressor function of Msx1 in cell cycle progression.
National Creative Research Initiatives Center for ARS Network, Department of Obstetrics and Gynecology, Molecular Therapy Research Center, Samsung Medical Center, Sungkyunkwan University, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.
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Lee
D002455:Cell Division; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D005260:Female; D016193:G1 Phase; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051957:MSX1 Transcription Factor; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D016213:Cyclins; D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases