Estrogen Induces Metastatic Potential of Papillary Thyroid Cancer Cells through Estrogen Receptorαandβ

Abstract

Estradiol (E2) promotes metastatic propensity. However, the detailed mechanism remains largely unknown. E-cadherin, vimentin, and MMP-9 play a dominant role in the metastatic process. We aimed to investigate the effects of E2 on metastatic potential of PTC cell line BCPAP and on E-cadherin, vimentin, and MMP-9 protein expression. PTC cell line BCPAP was evaluated for the presence of estrogen receptor (ER) by western blot analysis. The effects of E2, PPT (a potent ERα-selective agonist), and DPN (a potent ERβ-selective agonist) on modulation of metastatic phenotype were determined by using in vitro scratch wound assay and invasion assay. In addition, the effects on E-cadherin, vimentin, and matrix metalloproteinase-9 (MMP-9) protein expression were evaluated by Western blot analysis. We found that BCPAP cells expressed ERα and ERβ. E2 and PPT enhanced, but DPN inhibited, the migration and invasion of BCPAP cells in an in vitro experimental model system that is modulated by E-cadherin, vimentin, and MMP-9. These findings indicate that E2 induces the metastatic potential of BCPAP cells through ERα and ERβ. The two ER subtypes play differential roles in modulation of BCPAP cell metastasis and the related molecule expressions including E-cadherin, vimentin, and MMP-9.

Matrix Metalloproteinases 2 and 9 and E-Cadherin Expression in the Endometrium During the Implantation Window of Infertile Women Before In Vitro Fertilization Treatment

“…Also, the loss of E-cadherin function is a causal factor in the promotion of invasion and metastasis. 33 High levels of soluble E-cadherin in serum 34 and urine 35 of patients with cancer and coexpression of MMPs and E-cadherin cell metastasis studies 36 support that statement. Based on animal studies, and the role of MMPs and E-cadherin in modulation mechanism of cancer invasion, we hypothesized that MMP-2, MMP-9, and E-cadherin can be expressed in the endometrium during the implantation window and are involved in the implantation process in women.…”

Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

“…It is known that estrogens can regulate thyroid cell proliferation by binding to both estrogen receptors (ERs), ERa (ESR1) and ERb (ESR2), and displaying different effects on cell survival and proliferation. In particular, a proliferative and anti-apoptotic effect and a role in metastatization have been shown for ERa, whereas ERb has a differentiative and pro-apoptotic action (3,4). Upon activation by estradiol (E 2 ), ER translocates to the nucleus and activates gene transcription.…”

“…Upon activation by estradiol (E 2 ), ER translocates to the nucleus and activates gene transcription. In thyroid cancer cell lines, the proliferative effects of estrogen were found to be mediated through the regulation of genes involved in growth control, such as bcl-2, Bax, c-fos, E-cadherin, and vimentin (4,5,6). Alternatively, E 2 activation leads to a 'non-genomic' action by ER, which includes a rapid activation of the intracellular ERK-1/2 and PI3K/Akt signaling pathways (7).…”

Increased vimentin mRNA expression in MCF-7 breast cancer cell line after repeated endoxifen-treatment

“…Previous results had shown that addition of β-estradiol could increase vimentin expression. Experiments conducted by Dong et al 20 demonstrated that estrogen could induce metastatic potential of thyroid cancer cells by increasing vimentin mRNA expression. Jimenez-Salazar et al 21 showed that 1 nM β-estradiol elicit c-Src activation after 15 minutes.…”