Profiling estrogen-regulated gene expression changes in normal and malignant human ovarian surface epithelial cells

Area of Science:

• Endocrinology
• Molecular Biology
• Oncology

Background:

• Estrogens influence both normal ovarian surface epithelium (OSE) cell function and epithelial ovarian cancer (OCa) development.
• The precise mechanisms underlying these dual roles of estrogens remain largely unknown.

Purpose of the Study:

• To investigate the differential effects of estradiol-17beta (E2) on gene expression in normal human ovarian surface epithelial (HOSE) cells versus ovarian cancer (OVCA) cells.
• To identify specific genes that exhibit opposing responses to E2 in normal and malignant ovarian epithelial cells.

Main Methods:

• Transcriptional profiling using cDNA microarrays to analyze gene expression changes in HOSE and OVCA cell lines treated with E2.
• In silico analysis to identify estrogen response elements (EREs) in gene promoters.
• Functional studies to assess the oncogenic or tumor-suppressive roles of identified genes in OVCA cells.

Main Results:

• E2 altered the expression of 155 genes in HOSE cells and 315 genes in OVCA cells, with only 19 overlapping genes.
• Five overlapping genes (RNPS1, ADD1, PLXNA3, SKIIP, rap-2) showed discordant E2 responses between HOSE and OVCA cells.
• RNPS1 and ADD1 demonstrated antitumor effects, PLXNA3 inhibited invasiveness, rap-2 promoted oncogenesis, and SKIIP promoted anchorage-independent growth in OVCA cells.

Conclusions:

• E2 acts on distinct transcriptomes in HOSE and OVCA cells, explaining its paradoxical roles.
• Differential E2 responses in overlapping genes identify potential oncogenes and tumor suppressors, offering insights into OCa regulation.