title: The cancer marker neutrophil gelatinase-associated lipocalin is highly expressed in human endometrial hyperplasia.
abstract: Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = -0.42 and r = -0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma.
authors.affiliation: Institute of Biochemical Science, College of Life Science, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Chi-Jr
authors.initials: CJ
authors.lastname: Liao
authors.forename: Yen Hua
authors.initials: YH
authors.lastname: Huang
authors.forename: Heng-Kien
authors.initials: HK
authors.lastname: Au
authors.forename: Le-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Sin-Tak
authors.initials: ST
authors.lastname: Chu
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004714:Endometrial Hyperplasia / Q000378:metabolism*; D004715:Endometriosis / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D017931:DNA Primers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D014746:Vimentin; D051176:beta Catenin; D051546:Cyclooxygenase 2