No evidence for promoter region methylation of the succinate dehydrogenase and fumarate hydratase tumour suppressor genes in breast cancer

被引：11
作者：
Huang K. [1 ,2 ]
Dobrovic A. [1 ,2 ]
Fox S. [1 ,2 ]
机构：
[1] Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne
[2] Departmant of Pathology, University of Melbourne, Parkville
来源：
BMC Research Notes | / 2卷 / 1期
关键词：
Breast Carcinoma; Promoter Methylation; Invasive Breast Carcinoma; Prolyl Hydroxylase; Fumarate Hydratase;
D O I：
10.1186/1756-0500-2-194
中图分类号：
学科分类号：
摘要：
Background. Succinate dehydrogenase (SDH) and fumarate hydratase (FH) are tricarboxylic acid (TCA) cycle enzymes that are also known to act as tumour suppressor genes. Increased succinate or fumarate levels as a consequence of SDH and FH deficiency inhibit hypoxia inducible factor-1 (HIF-1) prolyl hydroxylases leading to sustained HIF-1 expression in tumours. Since HIF-1 is frequently expressed in breast carcinomas, DNA methylation at the promoter regions of the SDHA, SDHB, SDHC and SDHD and FH genes was evaluated as a possible mechanism in silencing of SDH and FH expression in breast carcinomas. Findings. No DNA methylation was identified in the promoter regions of the SDHA, SDHB, SDHC, SDHD and FH genes in 72 breast carcinomas and 10 breast cancer cell lines using methylation-sensitive high resolution melting which detects both homogeneous and heterogeneous methylation. Conclusion. These results show that inactivation via DNA methylation of the promoter CpG islands of SDH and FH is unlikely to play a major role in sporadic breast carcinomas. © 2009 Fox et al; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 27 条
  • [1] Harris A.L., Hypoxia - A key regulatory factor in tumour growth, Nature Reviews Cancer, 2, 1, pp. 38-47, (2002)
  • [2] Semenza G.L., Targeting HIF-1 for cancer therapy, Nature Reviews Cancer, 3, 10, pp. 721-732, (2003)
  • [3] Yamamoto Y., Ibusuki M., Okumura Y., Kawasoe T., Kai K., Iyama K., Iwase H., Hypoxia-inducible factor 1 alpha is closely linked to an aggressive phenotype in breast cancer, Breast Cancer Research and Treatment, 110, 3, pp. 465-475, (2008)
  • [4] Unruh A., Ressel A., Mohamed H.G., Johnson R.S., Nadrowitz R., Richter E., Katschinski D.M., Wenger R.H., The hypoxia-inducible factor-1 alpha is a negative factor for tumor therapy, Oncogene, 22, 21, pp. 3213-3220, (2003)
  • [5] Fox S.B., Generali D.G., Harris A.L., Breast tumour angiogenesis, Breast Cancer Research, 9, 6, (2007)
  • [6] King A., Selak M.A., Gottlieb E., Succinate dehydrogenase and fumarate hydratase: Linking mitochondrial dysfunction and cancer, Oncogene, 25, 34, pp. 4675-4682, (2006)
  • [7] Gottlieb E., Tomlinson I.P., Mitochondrial tumour suppressors: A genetic and biochemical update, Nat Rev Cancer, 5, 11, pp. 857-866, (2005)
  • [8] Selak M.A., Armour S.M., MacKenzie E.D., Boulahbel H., Watson D.G., Mansfield K.D., Pan Y., Simon M.C., Thompson C.B., Gottlieb E., Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase, Cancer Cell, 7, 1, pp. 77-85, (2005)
  • [9] Eng C., Kiuru M., Fernandez M.J., Aaltonen L.A., A role for mitochondrial enzymes in inherited neoplasia and beyond, Nat Rev Cancer, 3, 3, pp. 193-202, (2003)
  • [10] Pollard P.J., Wortham N.C., Tomlinson I.P.M., The TCA cycle and tumorigenesis: The examples of fumarate hydratase and succinate dehydrogenase, Annals of Medicine, 35, 8, pp. 634-635, (2003)
123