title: Expression and potential role of apolipoprotein D on the death-survival balance of human colorectal cancer cells under oxidative stress conditions.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Biología y Genética Molecular-Departamento de Bioquímica y Biología Molecular y Fisiología, Universidad de Valladolid-CSIC, c/ Sanz y Forés 3, 47003, Valladolid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bajo-Grañeras
authors.forename: Jesús
authors.initials: J
authors.lastname: Crespo-Sanjuan
authors.forename: Rosa M
authors.initials: RM
authors.lastname: García-Centeno
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Garrote-Adrados
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gutierrez
authors.forename: Manuel
authors.initials: M
authors.lastname: García-Tejeiro
authors.forename: Beatriz
authors.initials: B
authors.lastname: Aguirre-Gervás
authors.forename: María D
authors.initials: MD
authors.lastname: Calvo-Nieves
authors.forename: Rosa
authors.initials: R
authors.lastname: Bustamante
authors.forename: Maria D
authors.initials: MD
authors.lastname: Ganfornina
authors.forename: Diego
authors.initials: D
authors.lastname: Sanchez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D053399:Apolipoproteins D / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors
chemical_list: D000975:Antioxidants; D053399:Apolipoproteins D; D017382:Reactive Oxygen Species