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 journalArticle

32 Citations (Scopus)

Abstract

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
Volume195
Issue number2
DOIs
Publication statusPublished - 2007 Nov 1

Fingerprint

Estrogen Receptors
Apoptosis
Growth
Neoplasms
Estrogens
Transcription Factor AP-1
Medullary Thyroid cancer
Infection
Mitotic Index

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Cho, Mi Ae ; Lee, Mi Kyung ; Nam, Kee Hyun ; Chung, Woung Youn ; Park, Cheong Soo ; Lee, Ju Hyeong ; Noh, Taewoong ; Yang, Woo Ick ; Rhee, Yumie ; Lim, Sung Kil ; Lee, Hyun Chul ; Lee, Eun Jig. / Expression and role of estrogen receptor α and β in medullary thyroid carcinoma : Different roles in cancer growth and apoptosis. In: Journal of Endocrinology. 2007 ; Vol. 195, No. 2. pp. 255-263.
@article{8a09a99ae8b74e32a105601a9cd9ef2f,
title = "Expression and role of estrogen receptor α and β in medullary thyroid carcinoma: Different roles in cancer growth and apoptosis",
abstract = "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.",
author = "Cho, {Mi Ae} and Lee, {Mi Kyung} and Nam, {Kee Hyun} and Chung, {Woung Youn} and Park, {Cheong Soo} and Lee, {Ju Hyeong} and Taewoong Noh and Yang, {Woo Ick} and Yumie Rhee and Lim, {Sung Kil} and Lee, {Hyun Chul} and Lee, {Eun Jig}",
year = "2007",
month = "11",
day = "1",
doi = "10.1677/JOE-06-0193",
language = "English",
volume = "195",
pages = "255--263",
journal = "Journal of Endocrinology",
issn = "0022-0795",
publisher = "Society for Endocrinology",
number = "2",

}

Expression and role of estrogen receptor α and β in medullary thyroid carcinoma : Different roles in cancer growth and apoptosis. / Cho, Mi Ae; Lee, Mi Kyung; Nam, Kee Hyun; Chung, Woung Youn; Park, Cheong Soo; Lee, Ju Hyeong; Noh, Taewoong; Yang, Woo Ick; Rhee, Yumie; Lim, Sung Kil; Lee, Hyun Chul; Lee, Eun Jig.

In: Journal of Endocrinology, Vol. 195, No. 2, 01.11.2007, p. 255-263.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression and role of estrogen receptor α and β in medullary thyroid carcinoma

T2 - Different roles in cancer growth and apoptosis

AU - Cho, Mi Ae

AU - Lee, Mi Kyung

AU - Nam, Kee Hyun

AU - Chung, Woung Youn

AU - Park, Cheong Soo

AU - Lee, Ju Hyeong

AU - Noh, Taewoong

AU - Yang, Woo Ick

AU - Rhee, Yumie

AU - Lim, Sung Kil

AU - Lee, Hyun Chul

AU - Lee, Eun Jig

PY - 2007/11/1

Y1 - 2007/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=36348962973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348962973&partnerID=8YFLogxK

U2 - 10.1677/JOE-06-0193

DO - 10.1677/JOE-06-0193

M3 - Article

C2 - 17951536

AN - SCOPUS:36348962973

VL - 195

SP - 255

EP - 263

JO - Journal of Endocrinology

JF - Journal of Endocrinology

SN - 0022-0795

IS - 2

ER -