Overexpression of estrogen receptor-α in the endometrial carcinoma cell line Ishikawa: Inhibition of growth and angiogenic factors

Syed Hamid Ali, Amy L. O'Donnell, Seema Mohamed, Shaker Mousa, Paresh Dandona

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

A high level of estrogen receptor-α (ER-α) is believed to be favorable in the prognosis and treatment of endometrial, ovarian, and breast cancer. High levels of ER-α have been shown to inhibit the growth and invasive, metastatic potential of breast cancer cell lines. To bring about these inhibitory effects, ER-α probably acts through other cellular factors involved in the regulation of cell growth. To investigate the role of high levels ER-α in growth inhibition of endometrial cancer cells. A human ER-α cDNA was stably overexpressed in an endometrial cancer cell line, namely, Ishikawa. ER-α-overexpressing, parent, and control Ishikawa cells were grown in vitro and their growth rates were compared by cell count. ER-α-overexpressing and parent Ishikawa cells were also grown in vitro as tumors in a chicken chorioallantoic membrane (CAM) model, and tumor growth and angiogenesis was measured. Finally, levels of angiogenesis-modulating factors, nitric oxide synthase (NOS), and vascular endothelial growth factor (VEGF) were examined in relation to ER overexpression. The growth of Ishikawa cells was found inhibited in culture as well as in the CAM model. Angiogenesis of CAM tumors was also found inhibited in ER-overexpressing cells. Angiogenic factor VEGF was inhibited whereas the activity of NOS was found elevated following ER overexpression. Our work on the Ishikawa cell line indicates that high levels of ER-α in endometrial cancer may inhibit cancer growth by modulating angiogenic factors, thereby limiting the blood supply to the growing tumor. Our results support the earlier data from other groups that have shown a positive correlation between high ER content and better prognosis of endometrial cancers.

Original languageEnglish
Pages (from-to)637-645
Number of pages9
JournalGynecologic Oncology
Volume95
Issue number3
DOIs
Publication statusPublished - Dec 1 2004

Keywords

  • Endometrial cancer
  • Estrogen
  • Estrogen receptor
  • Ishikawa cells
  • Nitric oxide
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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