UHRF1 confers radioresistance to human breast cancer cells.

Abstract

PURPOSE:

To investigate the effect of ubiquitin-like with plant homeodomain (PHD) and ring finger domains 1 (UHRF1) overexpression on radiosensitivity to X-rays in human breast cancer MDA-MB-231 cells.

MATERIALS AND METHODS:

Cell survival was determined by colony formation assay; cell cycle distribution was measured by flow cytometry; apoptosis was evaluated by DNA fragmentation assay and Annexin V apoptosis detection kit; protein expression was analysed by Western blot assay; chromosome aberrations (centric rings and dicentrics) were assayed by conventional chromosome analysis.

RESULTS:

A significant decrease of radiosensitivity to X-rays was observed in MDA-MB-231 cells transfected with a full-length of human UHRF1 cDNA (MDA-MB-231/UHRF1) compared to the control cells (MDA-MB-231/parental and MDA-MB-231/pcDNA3 [mammalian expression vector]), and the similar results were observed in MDA-MB-468 cells. In contrast, a decreased expression of UHRF1 by a specific UHRF1-small interfering RNA (siRNA) significantly enhanced cell radiosensitivity. The UHRF1-mediated radioresistance was correlated with a G2(Ra)/M arrest, a decreased induction of apoptosis, a down-regulation of the pro-apoptotic protein anti-B cell lymphoma/leukemia 2 (bcl-2) associated X protein (Bax) and a up-regulation of the DNA damage repair proteins Lupus Ku autoantigen protein p70 (Ku-70) and Lupus Ku autoantigen protein p80 (Ku-80). Furthermore, chromosomal aberrations (centric rings and dicentrics) by X-rays were less in MDA-MB-231/UHRF1 than in MDA-MB-231/parental and MDA-MB-231/pcDNA3 control cells.

CONCLUSIONS:

These results suggested that UHRF1 may be a new target in the radiotherapy of breast cancer via affecting apoptosis and DNA damage repair.

• Authors: Xinli Li, Qinghui Meng, Eliot M Rosen, Saijun Fan
• Journal: International journal of radiation biology (Int J Radiat Biol) Vol. 87 Issue 3 Pg. 263-73 (Mar 2011) ISSN: 1362-3095 [Electronic] England
• PMID: 21067293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antigens, Nuclear
• BAX protein, human
• CCAAT-Enhancer-Binding Proteins
• DNA-Binding Proteins
• Nuclear Proteins
• bcl-2-Associated X Protein
• UHRF1 protein, human
• Ubiquitin-Protein Ligases
• Uhrf1 protein, mouse
• Xrcc6 protein, human
• Xrcc6 protein, mouse
• Ku Autoantigen

Topics

• Animals
• Annexin A5 (pharmacology)
• Antigens, Nuclear (pharmacology)
• Apoptosis
• Breast Neoplasms (drug therapy, radiotherapy)
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Cell Line, Tumor
• DNA Fragmentation
• DNA-Binding Proteins (pharmacology)
• Drug Resistance, Neoplasm
• Flow Cytometry (methods)
• Humans
• Ku Autoantigen
• Mice
• Nuclear Proteins (metabolism)
• Radiation Tolerance
• Ubiquitin-Protein Ligases
• bcl-2-Associated X Protein (metabolism)