Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions
| Autor: | Raquel Bajo-Grañeras, Rosa M. García-Centeno, Beatriz Aguirre-Gervás, Gabriel Gutiérrez, José Antonio Garrote-Adrados, Maria D. Ganfornina, Diego Sanchez, María D. Calvo-Nieves, Jesús Crespo-Sanjuán, Rosa Bustamante, Manuel García-Tejeiro |
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| Přispěvatelé: | Junta de Castilla y León, Ministerio de Educación y Ciencia (España), Ministerio de Ciencia e Innovación (España) |
| Rok vydání: | 2013 |
| Předmět: |
Male
Apolipoprotein D Predictive marker Apoptosis Lipocalin Antioxidants Risk Factors Intestinal Mucosa Aged 80 and over DNA methylation Cell Death Gastroenterology Middle Aged Gene Expression Regulation Neoplastic Colón - Cáncer - Tratamiento Disease Progression Female Colorectal Neoplasms HT29 Cells Adult medicine.medical_specialty Stromal cell Cell Survival Lipid peroxidation Down-Regulation Biology Polymorphism Single Nucleotide Internal medicine medicine Humans Genetic Predisposition to Disease Apolipoproteins D Aged Cell Proliferation Neoplasm Staging Tumor microenvironment Gene Expression Profiling Cancer medicine.disease Oxidative Stress Endocrinology Tumor progression Colorectal cancer stages Cancer research Lipid Peroxidation Reactive Oxygen Species |
| Zdroj: | UVaDOC. Repositorio Documental de la Universidad de Valladolid instname Digital.CSIC. Repositorio Institucional del CSIC |
| Popis: | et al. [Purpose]: Inverse correlations of apolipoprotein D (ApoD) expression with tumor growth have been shown, therefore proposing ApoD as a good prognostic marker for diverse cancer types, including colorectal cancer (CRC). Besides, ApoD expression is boosted upon oxidative stress (OS) in many pathological situations. This study aims at understanding the role of ApoD in the progression of human CRC. [Methods]: Samples of CRC and distant normal tissue (n = 51) were assayed for levels of lipid peroxidation, expression profile of OS-dependent genes, and protein expression. Three single-nucleotide polymorphisms in the ApoD gene were analyzed (n = 139), with no significant associations found. Finally, we assayed the effect of ApoD in proliferation and apoptosis in the CRC HT-29 cell line. [Results]: In CRC, lipid peroxides increase while ApoD messenger RNA and protein decrease through tumor progression, with a prominent decrease in stage I. In normal mucosa, ApoD protein is present in lamina propia and enteroendocrine cells. In CRC, ApoD expression is heterogeneous, with low expression in stromal cells commonly associated with high expression in the dysplastic epithelium. ApoD promoter is basally methylated in HT-29 cells but retains the ability to respond to OS. Exogenous addition of ApoD to HT-29 cells does not modify proliferation or apoptosis levels in control conditions, but it promotes apoptosis upon paraquat-induced OS. [Conclusion]: Our results show ApoD as a gene responding to OS in the tumor microenvironment. Besides using ApoD as marker of initial stages of tumor progression, it can become a therapeutic tool promoting death of proliferating tumor cells suffering OS. © 2013 Springer-Verlag Berlin Heidelberg. This work has been supported by grants to M.D.G. and D.S. (Ministerio de Educación y Ciencia (MEC), Spain, grant BFU2005-00522; Junta de Castilla y León (JCyL), grant VA049A05; and Ministerio de Ciencia e Innovación (MICINN), grant BFU2008-01170); and to R.B. (JCyL, GRS/278/A/08). |
| Databáze: | OpenAIRE |
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