Netrin-1 overexpression is predictive of ovarian malignancies

Oncotarget. 2011 May;2(5):363-7. doi: 10.18632/oncotarget.258.

Abstract

Netrin-1 (NTN1) is functionally important for the development of the nervous system.Interestingly, few recent studies showed that NTN1 may also promote cancer by increasing survival and resistance of lung and breast cancer cells to apoptosis. Our purpose was to investigate whether NTN1 and its receptor DCC may be involved in ovarian cancer. The NTN1 and DCC mRNAs were quantified by real-time RTPCR in normal (10), benign (8) and cancer (17) ovarian tissues. ALAS1 and TBP housekeeping genes were used for normalization. NTN1 was found overexpressed in 76% of ovarian cancer specimens (13/17) as compared to normal (0/10, p<0.004)and benign (1/8, p<0.008) samples. Increased NTN1 mRNA levels correlated with advanced tumor stage (stage III, n=8, 100%) and grade (grade 3, n=7, 100%). In contrast, DCC was found downregulated in 59% (10/17) of ovarian tumors tested but correlation was not significant when compared to normal or benign specimens. Here,we demonstrated that NTN1 may be involved in ovarian cancer as the expression of NTN1 mRNA is strongly upregulated in ovarian malignant tumors but not in benign tumors. The fact that increased NTN1 is specifically observed in cancerous tissues indicates that NTN1 may represent a novel candidate biomarker for ovarian cancer.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • DCC Receptor
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Nervous System / embryology
  • Nervous System / growth & development
  • Nervous System / metabolism*
  • Netrin-1
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / physiopathology
  • Ovary / metabolism*
  • Ovary / pathology
  • Prognosis
  • Protein Binding
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Biomarkers, Tumor
  • DCC Receptor
  • DCC protein, human
  • NTN1 protein, human
  • Nerve Growth Factors
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Netrin-1