Tamoxifen-Dependent Induction of AGR2 Is Associated with Increased Aggressiveness of Endometrial Cancer Cells

Cancer Invest. 2017 May 28;35(5):313-324. doi: 10.1080/07357907.2017.1309546. Epub 2017 Apr 12.

Abstract

Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.

Keywords: AGR2; Breast cancer; Endometrial cancer; Tamoxifen.

MeSH terms

  • A549 Cells
  • Adenocarcinoma / chemically induced*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Antineoplastic Agents, Hormonal / toxicity*
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cell Transformation, Neoplastic / chemically induced*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Endometrial Neoplasms / chemically induced*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Humans
  • MCF-7 Cells
  • Mucoproteins
  • Neoplasm Invasiveness
  • Oncogene Proteins
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Interference
  • Retrospective Studies
  • Risk Factors
  • Signal Transduction / drug effects
  • Tamoxifen / toxicity*
  • Transfection
  • Up-Regulation

Substances

  • AGR2 protein, human
  • Antineoplastic Agents, Hormonal
  • Mucoproteins
  • Oncogene Proteins
  • Proteins
  • Tamoxifen