Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β

  • Authors: Akhilesh Kumar, Carolyn M. Klinge, Richard E. Goldstein
  • View Affiliations

  • Published online on: Saturday, May 1, 2010
  • Pages: 1067-1080
  • DOI: 10.3892/ijo_00000588

Abstract

Premenopausal women are at highest risk for papillary and follicular thyroid carcinoma, implicating a role for estrogens in thyroid cancer. The expression of estrogen receptors α and β (ER), the effects of estradiol (E2), selective estrogen receptor modulators (SERMs) 4-hydroxytamoxifen and raloxifene, and ER subtype selective agonists were examined in NPA87 and KAT5 papillary and WRO follicular thyroid carcinoma cell lines. All three thyroid cancer cell lines expressed full-length ERα and ERβ proteins with cytoplasmic localization that was unaffected by E2. ICI 182,780 (Fulvestrant, an ER antagonist), and inhibitors of non-genomic E2-activated MAPK and PI3K signaling blocked E2-induced cell proliferation. SERMs acted in a cell line-specific manner. No E2-induced estrogen response element (ERE)-driven reporter activity was observed in transiently transfected thyroid cancer cells. However, E2 increased transcription of established endogenous E2-target genes, i.e., cathepsin D in WRO and cyclin D1 in both KAT5 and WRO cells in an ER-dependent manner as validated by inhibitor and siRNA experiments. In contrast, E2 did not increase progesterone receptor expression in the thyroid cancer cell lines. E2 stimulated phosphorylation of ERK1/2 in KAT5 and WRO cells and siERα or siERβ inhibited E2-induced ERK phosphorylation. Expression of the putative membrane estrogen receptor GPR30 was detected in WRO, but not NPA87 or KAT5 cells. GPR30 expression was lower in WRO than MCF-7 human breast cancer cells. Overall, these findings suggest E2-mediated thyroid cancer cell proliferation involves ERα and ERβ transcriptional and non-genomic signaling events.
Journal Cover

May 2010
Volume 36 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Kumar, A., Klinge, C., & Goldstein, R. (2010). Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β. International Journal of Oncology, 36(5), 1067-1080.
MLA
Kumar, Klinge, and Richard Goldstein. "Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β." International Journal of Oncology International Journal of Oncology 36.5 (2010): 1067-1080.
Chicago
Kumar, Klinge, and Richard Goldstein. "Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β." International Journal of Oncology International Journal of Oncology 36 no. 5 (2010): 1067-1080.