ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer
Open Access
- 1 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 104 (4), 700-706
- https://doi.org/10.1038/sj.bjc.6606012
Abstract
We have demonstrated for the first time that a novel human AlkB homologue, ALKBH3, contributes to prostate cancer development, but its clinical and biological roles in lung cancer remain unclear. Expression of both mRNA and protein of PCA-1 was examined by RT–PCR and western blotting. We also assessed association with senescence and in vivo ALKBH3 treatment on orthotopic tumour cell inoculation, and analysed it clinicopathologically. We have since found novel biological roles for ALKBH3 in human lung cancers, particularly in adenocarcinoma. Our immunohistochemical analysis of human adenocarcinomas and squamous cell carcinomas of the lung not only showed overexpression of ALKBH3 in these tumours but the percentage of cells positive for ALKBH3 also correlated statistically to recurrence-free survival in adenocarcinoma. Knockdown of ALKBH3 by siRNA transfection induced expression of p21WAF1/Cip1 and p27Kip1 in the human lung adenocarcinoma cell line A549, resulting in cell cycle arrest, senescence and strong suppression of cell growth in vitro. In vivo, peritoneal tumour growth and dissemination was inhibited in nude mice, previously inoculated with the A549 cell line, by intraperitoneal injection of ALKBH3 siRNA + atelocollagen, as demonstrated by the reduction in both number and diameter of tumours developing in the peritoneum. We suggest that ALKBH3 contributes significantly to cancer cell survival and may be a therapeutic target for human adenocarcinoma of the lung.Keywords
This publication has 48 references indexed in Scilit:
- Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specificationNature, 2010
- Healing and Hurting: Molecular Mechanisms, Functions, and Pathologies of Cellular SenescenceMolecular Cell, 2009
- Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1Science, 2009
- Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLCBritish Journal of Cancer, 2008
- Trends in Lung Cancer Incidence by Histological Type in Osaka, JapanJapanese Journal of Clinical Oncology, 2008
- The Obesity-AssociatedFTOGene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid DemethylaseScience, 2007
- Prostate cancer antigen‐1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancerCancer Science, 2007
- Epidermal growth factor receptor mutations in lung cancerNature Reviews Cancer, 2007
- The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamilyBMC Biochemistry, 2007
- Chemotherapeutic Approaches for Targeting Cell Death PathwaysThe Oncologist, 2006