Expression and role of estrogen receptor α and β in medullary thyroid carcinoma: Different roles in cancer growth and apoptosis

Mi Ae Cho, Mi Kyung Lee, Kee Hyun Nam, Woung Youn Chung, Cheong Soo Park, Ju Hyeong Lee, Taewoong Noh, Woo Ick Yang, Yumie Rhee, Sung Kil Lim, Hyun Chul Lee, Eun Jig Lee

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Medullary thyroid carcinoma (MTC) originates from parafollicular C cells. Estrogen receptor β (ERβ) expression was detected in normal parafollicular C cells and MTC tumor tissue, but ERα expression in MTC tumors still remains undetermined. The appearance and loss of ERα or ERβ expression has been known to play a role in the development and progression of many human cancers. We performed immunohistochemical studies of ERα, EROβ, and Ki67, a mitotic index, in 11 human MTC tissue samples. ERCα was detected in 10 cases (91%), and ERβ expression was observed in 8 cases (72.7%). A majority (8/10) of ERα-positive tumors showing ERβ Ki67 expression was detected in three cases (27.3%). Neither clinical parameters nor tumor node metastasis (TNM) tumor staging was correlated with the positivity for ERs or Ki67. To investigate the biological role of each ER, we used ER-negative MTC TT cells and adenoviral vectors carrying ERα (Ad-ERα), ERβ (Ad-ERβ), estrogen response element (ER-E)-Luc (Ad-ER-E-Luc), and activator protein 1 (AP1)-Luc (Ad-AP1-Luc). Estrogen stimulated and anti-estrogen, ICI 182 780, suppressed ERE reporter activity in TT cells expressing ERα or ERβ, suggesting that both ERs use the same classical ERE-mediated pathway. Ad-ERα infection stimulated TT cell growth; in contrast, Ad-ERβ infection suppressed their growth. Apoptosis was detected in Ad-ERβ-infected TT cells. Estrogen and anti-estrogen suppressed AP1 activity in Ad-ERα-infected cells, whereas upon Ad-ERβ infection estrogen further stimulated AP1 activity which in turn is suppressed by anti-estrogen, suggesting that each ER acts dfferendy through a non-ER-Emediated pathway. Our results suggest that ERα and ERα may play different roles in MTC tumor growth and progression.

Original languageEnglish
Pages (from-to)255-263
Number of pages9
JournalJournal of Endocrinology
Issue number2
Publication statusPublished - 2007 Nov

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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