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

Gynecol Oncol. 2013 Sep;130(3):601-8. doi: 10.1016/j.ygyno.2013.06.002. Epub 2013 Jun 10.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Cervical cancer; Radiation therapy; Radiosensitivity; RbAp48.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Caspase 8 / genetics
  • Cell Proliferation / radiation effects
  • Cell Survival / radiation effects
  • Female
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression / radiation effects*
  • Gene Silencing
  • HeLa Cells
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Radiation Tolerance*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma-Binding Protein 4 / genetics*
  • Retinoblastoma-Binding Protein 4 / metabolism*
  • Tumor Suppressor Protein p53 / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / radiotherapy

Substances

  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 4
  • Tumor Suppressor Protein p53
  • Caspase 8