title: The antitumor immunopreventive effects of a DNA vaccine against CYP26a1 on mouse breast carcinoma.
abstract: BACKGROUND
  CYP26a1, which functioned mainly as a retinoic acid (RA) catabolic enzyme, has been shown to be oncogenic and to support cell survival in many breast carcinoma cells.
  
  
  OBJECTIVE
  The purpose of the study was to investigate the antitumor effect of a DNA vaccine targeting CYP26a1 on breast tumors development in mice which highly express CYP26a1 and to further clarify its potential mechanism.
  
  
  METHODS
  After three times immunization of the DNA vaccine, the BALB/c mice were inoculated with the engineered 4T1 breast cancer cells expressing CYP26a1. Primary tumors were measured every 4 days after tumor cell inoculation. The primary tumors were surgically removed and weighted after 30 days of inoculation. The anti-CYP26a1 antibody titer of the antiserum was measured by an enzyme-linked immunosorbent assay (ELISA). The effect of the vaccine on apoptosis of the primary tumor was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Apoptosis-related proteins in primary tumor were detected by Western blotting. The expression of the Th1 and Th2 type cytokines was detected by RT-PCR.
  
  
  RESULTS
  The vaccine could elicit the production of anti-CYP26a1 antibody and significantly inhibit the growth of the primary tumor compared to the control groups (p<0.05). The vaccine induced the apoptosis of the primary tumor with the increase in expression of apoptosis-related proteins p53, Caspase3 and Fas. Furthermore, the vaccine increased the expression of the Th1 cytokine, but not the expression of Th2 cytokine.
  
  
  CONCLUSIONS
  Our study shows that the vaccine targeting CYP26a1 significantly inhibits the primary tumor growth and progression by activating the apoptosis pathway and by eliciting both humoral and cellular immune responses.
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1 Beichen West Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Rong-Chun
authors.initials: RC
authors.lastname: Wang
authors.forename: Zhen-Kun
authors.initials: ZK
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Jing-Pian
authors.initials: JP
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000072516:Retinoic Acid 4-Hydroxylase; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D019496:Cancer Vaccines; D019444:Vaccines, DNA; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase