Critical roles of LGN/GPSM2 phosphorylation by PBK/TOPK in cell division of breast cancer cells
| Autor: | Toyomasa Katagiri, Koji Ueda, Toshihiko Nishidate, Yusuke Nakamura, Chikako Fukukawa |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
genetic structures Cell division Blotting Western Mitosis Breast Neoplasms Biology Protein Serine-Threonine Kinases Immunoenzyme Techniques Breast cancer Western blot Cell Line Tumor Genetics medicine Phosphoprotein Phosphatases Humans Immunoprecipitation Northern blot RNA Messenger Phosphorylation RNA Small Interfering Metaphase Cell Proliferation Mitogen-Activated Protein Kinase Kinases medicine.diagnostic_test Kinase Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins medicine.disease Blotting Northern Midbody Mutation Cancer research Mutagenesis Site-Directed Female Cell Division |
| Zdroj: | Genes, chromosomescancer. 49(10) |
| ISSN: | 1098-2264 |
| Popis: | To investigate the molecular mechanism of mammary carcinogenesis and identify novel molecular targets for breast cancer therapy, we analyzed genome-wide gene expression profiles of 81 clinical breast cancer samples. Here, we report the critical role of LGN/GPSM2 (Leu-Gly-Asn repeat-enriched protein/G-protein signaling modulator 2) in the growth of breast cancer cells. Semiquantitative RT-PCR and Northern blot analyses confirmed upregulation of LGN/GPSM2 in a large proportion of breast cancers. Immunocytochemical staining identified LGN/GPSM2 at the spindle in cells at metaphase, and at midzone and midbody in cytokinetic cells. Western blot analysis indicated the highest expression and the phosphorylated form of LGN/GPSM2 protein in G2/M phase. Treatment with small-interfering RNAs (siRNAs) targeting LGN/GPSM2 caused incompletion of cell division and resulted in significant growth suppression of breast cancer cells. We found that the 450th threonine (Thr450) of LGN/GPSM2 was phosphorylated by the serine/threonine kinase PBK/TOPK during mitosis. Overexpression of LGN/GPSM2-T450A in which Thr450 was substituted with alanine induced growth suppression and aberrant chromosomal segregation. These findings imply an important role of LGN/GPSM2 in cell division of breast cancer cells and suggest that the PBK/TOPK-LGN/GPSM2 pathway might be a promising molecular target for treatment of breast cancer. © 2010 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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