The sulfatase pathway as estrogen supply in endometrial cancer

Steroids. 2018 Nov:139:45-52. doi: 10.1016/j.steroids.2018.09.002. Epub 2018 Sep 12.

Abstract

Objective: Contradictory results are reported about the level of steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1; together, the sulfatase pathway) and aromatase (CYP19A1) in endometrial cancer (EC). The aim of this study was to explore the levels of these enzymes in a well-characterized cohort of EC patients and postmenopausal controls.

Materials and methods: Endometrial tissues from 31 EC patients (21 grade 1 and 10 grade 2-3) and 19 postmenopausal controls were collected. Levels of mRNA (RT-qPCR) and protein (immunohistochemistry) were determined. STS enzyme activity was measured by HPLC, whereas SULT1E1 enzyme activity was determined using a novel method based on liquid chromatography-mass spectrometry (LC-MS/MS).

Results: No significant differences in STS, SULT1E1 mRNA or protein levels and STS:SULT1E1 ratio were found. STS enzyme activity and STS:SULT1E1 activity ratio were significantly decreased in ECs compared with controls. CYP19A1 mRNA levels were lower in ECs than in controls.

Conclusion: A novel highly sensitive and accurate protocol to assess SULT1E1 activity is presented. STS enzyme activity and the STS:SULT1E1 activity ratio seem to be lower in ECs than in controls. STS is an important route for estrogen supply in endometrial cells.

Keywords: Endometrial cancer; Estrogen metabolism; Estrogen sulfotransferase; Intracrinology; Steroid sulfatase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aromatase / genetics*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Endometrium / metabolism
  • Endometrium / pathology
  • Estrogens / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Postmenopause / blood
  • RNA, Messenger / genetics
  • Signal Transduction / genetics
  • Steryl-Sulfatase / genetics*
  • Sulfotransferases / genetics*

Substances

  • Estrogens
  • RNA, Messenger
  • Aromatase
  • CYP19A1 protein, human
  • Sulfotransferases
  • estrone sulfotransferase
  • STS protein, human
  • Steryl-Sulfatase