title: Effect of BRCA1 on epidermal growth factor receptor in ovarian cancer.
abstract: BACKGROUND
  Both BRCA1 and epidermal growth factor receptor (EGFR) play a critical role in ovarian cancer progression. However, the crosstalk between BRCA1 and EGFR signaling pathways in ovarian cancer remains largely unknown.
  
  
  METHODS
  The effect of BRCA1 on EGFR was assessed in 146 serous ovarian cancer patients (28 pairs of BRCA1-mutated or not, 23 pairs of BRCA2-mutated or not, and 22 pairs with hypermethylated BRCA1 promoter or not). BRCA1 promoter methylation was analyzed by bisulfite sequencing using primers flanking the core promoter region. Expression levels of BRCA1 and EGFR were assessed by immunohistochemistry and real-time PCR. The knockdown and overexpression of BRCA1 were achieved using a lentiviral vector in 293 T cells, SKOV3 ovarian cancer cells, and primary non-mutated and BRCA1-mutated ovarian cancer cells.
  
  
  RESULTS
  EGFR expression was increased in all cancer tissues compared to normal tissues. Additionally, EGFR expression was higher in normal tissues of BRCA1-mutated patients, and was further increased in cancer tissues; EGFR levels were also significantly elevated in ovarian cancer with promoter hypermethylation-mediated inactivation of BRCA1. BRCA1 knockdown was an effective way to activate EGFR expression in ovarian cancer cells.
  
  
  CONCLUSIONS
  These results indicate that BRCA1 may be a potential trigger in transcriptional regulation of EGFR in the development of ovarian cancer.
authors: Department of Obstetrics and Gynecology, Shengjing Hospital, China Medical University, No, 36, Sanhao Street, Heping District, Shenyang 110004, China. leeda@ymail.com.
authors: Da
authors: D
authors: Li
authors: Fang-Fang
authors: FF
authors: Bi
authors: Ji-Min
authors: JM
authors: Cao
authors: Chen
authors: C
authors: Cao
authors: Chun-Yan
authors: CY
authors: Li
authors: Qing
authors: Q
authors: Yang
mesh_terms: D019313:BRCA1 Protein / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D024682:BRCA2 Protein / Q000235:genetics; D019175:DNA Methylation; D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D019398:Genes, BRCA1; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C541485:EGFR protein, mouse; D066246:ErbB Receptors