PloS one, 2011-09, Vol.6 (9), p.e25343
2011
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Up-regulation of kin17 is essential for proliferation of breast cancer
- Ist Teil von
- PloS one, 2011-09, Vol.6 (9), p.e25343
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Kin17 is ubiquitously expressed at low levels in human tissue and participates in DNA replication, DNA repair and cell cycle control. Breast cancer cells are characterized by enabling replicative immortality and accumulated DNA damage. However, whether kin17 contributes to breast carcinogenesis remains unknown. In this study, we show for the first time that kin17 is an important molecule related to breast cancer. Our results show that kin17 expression was markedly increased in clinical breast tumors and was associated with tumor grade, Ki-67 expression, p53 mutation status and progesterone receptor expression, which were assessed in a clinicopathologic characteristics review. Knockdown of kin17 inhibited DNA replication and repair, blocked cell cycle progression and inhibited anchorage-independent growth, while increasing sensitivity to chemotherapy in breast cancer cells. Moreover, kin17 silencing decreased EGF-stimulated cell growth. Furthermore, overexpression of kin17 promoted DNA replication and cell proliferation in MCF-10A. Our findings indicate that up-regulation of kin17 is strongly associated with cellular proliferation, DNA replication, DNA damage response and breast cancer development. The increased level of kin17 was not only a consequence of immortalization but also associated with tumorigenesis. Therefore, kin17 could be a novel therapeutic target for inhibiting cell growth in breast cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0025343Titel-ID: cdi_plos_journals_1308858768
- Format
- –
- Schlagworte
- Adult, Biology, Biomarkers, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Cancer, Cancer therapies, Carcinogenesis, Carcinogens, Cell cycle, Cell Cycle - drug effects, Cell Cycle - genetics, Cell Line, Tumor, Cell proliferation, Cell Proliferation - drug effects, Chemotherapy, Damage accumulation, Deoxyribonucleic acid, Development and progression, Disease, Disease Progression, DNA, DNA biosynthesis, DNA damage, DNA repair, DNA Repair - drug effects, DNA Repair - genetics, DNA replication, DNA Replication - drug effects, DNA Replication - genetics, DNA-Binding Proteins - deficiency, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Education, Engineering, Epidermal growth factor, Epidermal Growth Factor - pharmacology, Epidermal growth factors, Female, Gene Knockdown Techniques, Health aspects, Humans, Immortalization, Inhibition, Ionizing radiation, Kinases, Laboratories, Life sciences, Mammals, Mammography, Medicine, Metabolism, Mutation, Ovarian cancer, p53 Protein, Pathogenesis, Physics, Progesterone, RecA protein, Repair, Replication, RNA-Binding Proteins - genetics, RNA-Binding Proteins - metabolism, Studies, Tumor proteins, Tumorigenesis, Tumors, Up-Regulation