Radiation-inducible protein RbAp48 contributes to radiosensitivity of cervical cancer cells

Department of Medical Microbiology, Shandong University School of Medical, Jinan, China.
Gynecologic Oncology (Impact Factor: 3.77). 06/2013; 130(3). DOI: 10.1016/j.ygyno.2013.06.002
Source: PubMed


Retinoblastoma-associated protein 48 (RbAp48) has been recently discovered as a radiosensitive gene. We aimed to investigate the role of RbAp48 in radiosensitivity of cervical cancer cells in vivo and in vitro.

We used real-time RT-PCR and Western blot assay to examine the expression of RbAp48 in irradiated cervical cancer cell lines, including SiHa, Caski, and HeLa cells. The role of RbAp48 in radiosensitivity of cervical cancer cells was assessed by cell proliferation, counting, survival, and apoptosis as well as cell cycle and tumor growth assays with RbAp48 overexpression or gene silencing.

The expression of RbAp48 was increased in irradiated cervical cancer cell lines. Overexpression of RbAp48 induced G2/M arrest and apoptosis in irradiated cells, which was related to upregulation of p53, Rb and caspase-8 expression. Adenovirus-RbAp48 infection and irradiation synergistically inhibited tumor growth in nude mice.

RbAp48 is a radiation-inducible gene in cervical cancer cells because of enhanced radiosensitivity of cervical cancer cells in vivo and in vitro. RbAp48 may be a potential target to improve the results of radiation therapy for patients with cervical cancer.

  • Source
    • "Cells in the G2/M phase are most sensitive to radiation whereas those in the S phase are resistant [19]. Researchers have achieved radiosensitization via cell cycle arrest in G2/M phase by taxanes or gene therapy [20, 21]. Apoptosis is the main mechanism of cell death after radiation, and the apoptosis index correlates positively with tumor radiosensitivity [22]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0-100 μ g/mL nedaplatin, and inhibitory effects on cell viability and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50 values of 34.32 and 63.69 μ g/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.
    Full-text · Article · May 2014 · BioMed Research International
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transcription regulation through chromatin compaction and decompaction is regulated through various chromatin-remodeling complexes such as nucleosome remodeling and histone deacetylation (NuRD) complex. NuRD is a 1 MDa multi-subunit protein complex which comprises many different subunits, among which histone deacetylases HDAC1/2, ATP-dependent remodeling enzymes CHD3/4, histone chaperones RbAp46/48, CpG-binding proteins MBD2/3, the GATAD2a (p66α) and/or GATAD2b (p66β) and specific DNA-binding proteins MTA1/2/3. Here, we review the currently known crystal and NMR structures of these subunits, the functional data and their relevance for biomedical research considering the implication of NuRD subunits in cancer and various other diseases. The complexity of this macromolecular assembly, and its poorly understood mode of interaction with the nucleosome, the repeating unit of chromatin, illustrate that this complex is a major challenge for structure-function relationship studies which will be tackled best by an integrated biology approach.
    No preview · Article · Mar 2015 · Cellular and Molecular Life Sciences CMLS
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Emerging evidence has indicated the significance of RbAp48 in tumorigenesis. Although many genetic and epigenetic factors have been found to be involved in the pathogenesis of hypopharyngeal carcinoma, the effect of RbAp48 in hypopharyngeal carcinoma is still unclear. Methods: A stable cell line overexpressing RbAp48 was generated in FaDu cells. Cell proliferation and colony formation were detected using FaDu-RbAp48 cells. Next we utilized nude mouse xenografts to determine the role of RbAp48. Flow cytometry was employed to investigate the effect of RbAp48 in cell cycle distribution and apoptosis. Real-time PCR was used to detect the expression of tumor suppressors and apoptosis-related factors. Results: The overexpression of RbAp48 inhibited cell proliferation, colony formation, and tumor formation in nude mice. The overexpression of RbAp48 affected cell cycle distribution and induced apoptosis. The expression of p53, Rb, Bax, caspase 3, caspase 8, and caspase 9 was upregulated, whereas the expression of Bcl-2 was downregulated resulting from the overexpression of RbAp48. Conclusion: RbAp48 was identified as critical in the proliferation of hypopharyngeal carcinoma in both in vitro and in vivo experiments. It is conceivable that the regulation of tumor suppressors (Bcl-2 family and caspase enzymes) by RbAp48 contributes, at least in part, to the RbAp48-mediated proliferation in hypopharyngeal carcinoma.
    No preview · Article · Sep 2015 · ORL