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: May 1, 2010     https://doi.org/10.3892/ijo_00000588
  • Pages: 1067-1080
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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.

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May 2010
Volume 36 Issue 5

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

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Spandidos Publications style
Kumar A, Klinge CM and Goldstein RE: Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β. Int J Oncol 36: 1067-1080, 2010.
APA
Kumar, A., Klinge, C.M., & Goldstein, R.E. (2010). Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β. International Journal of Oncology, 36, 1067-1080. https://doi.org/10.3892/ijo_00000588
MLA
Kumar, A., Klinge, C. M., Goldstein, R. E."Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β". International Journal of Oncology 36.5 (2010): 1067-1080.
Chicago
Kumar, A., Klinge, C. M., Goldstein, R. E."Estradiol-induced proliferation of papillary and follicular thyroid cancer cells is mediated by estrogen receptors α and β". International Journal of Oncology 36, no. 5 (2010): 1067-1080. https://doi.org/10.3892/ijo_00000588