Cytoplasmic Retention of CDC6 Induces Premature Senescence in Immortalized Cells and Suppresses Tumor Formation in Mice
Journal Title: Journal of Hematology and Oncology Research - Year 2016, Vol 2, Issue 2
Abstract
Senescence is a powerful mechanism that prevents the development of tumors in vivo; however, once tumors are formed, most are refractory to senescence in response to oncogenic stress. Therefore, a novel pathway leading to senescence is required. We herein demonstrated that the cell cycle regulator CDC6 translocated from the nucleus to the cytoplasm during senescence in a leptomycin B-resistant manner. In order to evaluate the translocation of CDC6, we utilized an estrogen receptor (ER) tag to retain CDC6 in the cytoplasm. ER-tagged CDC6 was exclusively cytoplasmic, inhibited cell proliferation, and induced senescence-associated (SA) b-galactosidase activity. Furthermore, ER-CDC6 inhibited the transformation of mouse fibroblasts by the active ras oncogene in vitro, and suppressed tumor formation in NOD-SCID mice. Thus, CDC6 may play a critical role in the regulation of senescence in the cytoplasm in order to counteract tumorigenesis.
Authors and Affiliations
Akihiro Ueda, Noriko Yoneda-Kato, Yuji Yamanaka, Ikuko Nakamae, Jun-ya Kato
Keywords
Related Articles
- EP ID EP249564
- DOI 10.14302/issn.2372-6601.jhor-16-1125
- Views 135
- Downloads 0
Diagnostics of Progressive Multifocal Leukoencephalopathy in a Patient with Concomitant Lymphoma Infiltration of Central Nervous System During R-CHOP Chemotherapy- A Case Presentation and Review of the Literature.
Progressive multifocal leukoencephalopathy (PML) is a rare complication associated, inter alia, with rituximab-based lymphoma treatment. PML diagnosis is made easier with the criteria recently published by the American A...
Early Detection of Post-transplant Lymphoproliferative Disorder by Head and Neck Manifestations
Introduction: Post-transplant lymphoproliferative disease (PTLD) is a collection of conditions associated with abnormal proliferation of lymphoid tissues in patients after solid organ transplants (SOT). Its clinical pre...
Unusual Cutaneous Toxicity After Prolonged Use of Hydroxyurea in Polycythemia Vera: A Case Report
Hydroxyurea (HU) is commonly used for the long-term treatment of patients with chronic myeloproliferative neoplasms. The drug is usually well tolerated in the large majority of subjects, although systemic and/or localize...
The Silver, Cobalt, Chromium, Iron, Mercury, Rubidium, Antimony, Selenium, and Zinc Contents in Human Bone Affected by Chondrosarcoma
Objectives: To clarify the role of trace elements in the etiology and the pathogenesis of the chondrosarcoma, a non-destructive neutron activation analysis with high resolution spectrometry of long-lived radionuclides we...
Itraconazole Prophylaxis for an Outbreak of Invasive Aspergillosis in a Hematology Ward after Hospital Construction Work
Objective: Hospital construction work, among other environmental factors, is a risk factor for invasive aspergillosis (IA). Methods: We retrospectively surveyed the incidence of IA in hematology-oncology patients befo...