Glycodelin reduces carcinoma-associated gene expression in endometrial adenocarcinoma cells

Am J Obstet Gynecol. 2005 Dec;193(6):1955-60. doi: 10.1016/j.ajog.2005.05.073.

Abstract

Objective: Glycodelin is a major secretory glycoprotein of differentiated endometrial epithelium, rarely expressed in proliferative endometrium or endometrial cancer. We aimed to elucidate its role in growth and gene expression of endometrial adenocarcinoma cells, and hypothesized that glycodelin affects cell growth and tumor-associated gene expression.

Study design: Endometrial adenocarcinoma HEC-1B cells were transfected with glycodelin cDNA in both antisense and sense orientations. Cellular morphology, cell proliferation, and gene expression were compared between native and transfected cells.

Results: Compared with native and antisense-transfected carcinoma cells, sense-transfected, glycodelin-producing carcinoma cells showed reduced proliferation, morphologic changes, and altered expression of cancer-related genes. Notably, anti-apoptotic Bcl-XL and MUC1 genes were down-regulated.

Conclusion: Reduction by glycodelin transfection of carcinoma cell proliferation and expression of MUC1 and Bcl-XL is significant because these genes are often overexpressed in human cancers--MUC1 is linked to invasive growth and metastases, and both confer resistance to chemotherapy. These results suggest a novel mechanism whereby malignant growth of endometrial adenocarcinoma cells is regulated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Antigens / metabolism
  • Antigens, Neoplasm
  • Antisense Elements (Genetics)
  • Cell Line, Tumor
  • Cell Proliferation
  • Down-Regulation / genetics
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glycodelin
  • Glycoproteins / genetics
  • Glycoproteins / metabolism
  • Glycoproteins / physiology*
  • Humans
  • Immunohistochemistry
  • Mucin-1
  • Mucins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Up-Regulation / genetics
  • bcl-X Protein / metabolism

Substances

  • Antigens
  • Antigens, Neoplasm
  • Antisense Elements (Genetics)
  • Glycodelin
  • Glycoproteins
  • MUC1 protein, human
  • Mucin-1
  • Mucins
  • PAEP protein, human
  • Pregnancy Proteins
  • bcl-X Protein