title: Subtype specific elevated expression of hyaluronidase-1 (HYAL-1) in epithelial ovarian cancer.
abstract: BACKGROUND
  Epithelial ovarian cancer (EOC) is morphologically heterogeneous being classified as serous, endometrioid, clear cell, or mucinous. Molecular genetic analysis has suggested a role for tumor suppressor genes located at chromosome 3p in serous EOC pathogenesis. Our objective was to evaluate the expression of HYAL1, located at chromosome 3p21.3, in these EOC subtypes, and to investigate its correlation with the expression of steroid hormone receptors.
  
  
  RESULTS
  We determined the mRNA expression of HYAL1, estrogen receptor (ER)-α, ERβ and progesterone receptor (PR) in EOC tumor samples and cell lines using quantitative RT-PCR. We also examined the expression of these genes in a publicly available microarray dataset. HYAL-1 enzyme activity was measured in EOC cell lines and in plasma samples from patients. We found that HYAL1 mRNA expression was elevated in clear cell and mucinous EOC tissue samples, but not in serous and endometrioid samples, normal ovaries or benign tumors. Similar results were obtained by two different techniques and with tissue sample cohorts from two independent institutions. Concordantly, HYAL1 mRNA levels and enzymatic activity were elevated only in EOC cell lines derived from clear cell and mucinous subtypes. We also showed that HYAL1 mRNA was inversely correlated to that of ERα specifically in clear cell and mucinous EOCs. Additionally, ectopic expression of ERα in a clear cell EOC cell line (ER- and PR-negative) induced 50% reduction of HYAL1 mRNA expression, supporting a role of ERα in HYAL1 gene regulation. Significantly, HYAL-1 activity was also high in the plasma of patients with these EOC subtypes.
  
  
  CONCLUSIONS
  This is the first report showing high HYAL-1 levels in EOC and demonstrating HYAL1 gene repression by ERα. Our results identify Hyaluronidase-1 as a potential target/biomarker for clear cell and mucinous EOCs and especially in tumors with low ERα levels.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada.
authors.forename: Paule Héléna
authors.initials: PH
authors.lastname: Yoffou
authors.forename: Lydia
authors.initials: L
authors.lastname: Edjekouane
authors.forename: Liliane
authors.initials: L
authors.lastname: Meunier
authors.forename: André
authors.initials: A
authors.lastname: Tremblay
authors.forename: Diane Michèle
authors.initials: DM
authors.lastname: Provencher
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Euridice
authors.initials: E
authors.lastname: Carmona
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000201:enzymology / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000201:enzymology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D017077:Culture Media, Conditioned; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000145:classification* / Q000201:enzymology* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000097:blood / Q000145:classification* / Q000201:enzymology* / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D017077:Culture Media, Conditioned; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone; D006821:Hyaluronoglucosaminidase