title: 17β-Oestradiol activates proteolysis and increases invasion through phosphatidylinositol 3-kinase pathway in human cervical cancer cells.
abstract: OBJECTIVE
  Despite evidence that oestrogen may play an important role in the carcinogenesis of cervical cancer, its action and mechanism in cervical cancer invasion are not well defined.
  
  
  METHODS
  The invasion induced by 17β-oestradiol (E2) was measured by invasion assay. Real-time polymerase chain reaction (PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and gelatin zymography were used to study the role of E2 on metastasis-related proteases. The signal pathway was also investigated.
  
  
  RESULTS
  E2 was found to significantly enhance the invasion of cervical cell lines including HeLa, CaSki and SiHa cells, but not C33A cells. Moreover, E2 10(-8)M increased the expression and activation of matrix metalloproteinases (MMP-2 and MMP-9) in HeLa and CaSki cells, as shown by real-time PCR, Western blot, ELISA and gelatin zymography. The expression of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2) was decreased significantly by E2. Pretreatment with GM6001 10 μM (total MMP inhibitor) or SB-3CT 20 μM (specific gelatinase inhibitor) blocked the pro-invasive effect of E2. E2 was found to induce invasion via the phosphatidylinositol 3-kinase (PI3K) signalling pathway.
  
  
  CONCLUSIONS
  E2 may contribute to cervical cancer metastasis through activation of proteolysis and increased invasion via the PI3K pathway.
authors.affiliation: Department of Gynecology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Libing
authors.initials: L
authors.lastname: Xiang
authors.forename: Duo
authors.initials: D
authors.lastname: Han
authors.forename: Xuxia
authors.initials: X
authors.lastname: Shen
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D059748:Proteolysis / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism
chemical_list: C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9