Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-β signaling pathway

Natsuka Goto, Hiromi Hiyoshi, Ichiaki Ito, Mai Tsuchiya, Yuka Nakajima, Junn Yanagisawa

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

In the later stages of breast cancer, estrogen receptor (ER)α-negative cancers typically have higher histological grades than ERα-positive cancers, and transforming growth factor (TGF)-β promotes invasion and metastasis. Our previous study indicated that ERα inhibited TGF-β signaling by inducing the degradation of Smad in an estrogen-dependent manner. In the present study, we report that the suppressive effects of ERα and estrogen on tumor progression are mediated by inhibiting TGF-β signaling. Furthermore, we investigated the effects of antiestrogens such as ICI182,780 (ICI) or tamoxifen (TAM) on TGF-β signaling and breast cancer invasiveness. The levels of total Smad and pSmad were reduced by estrogen, whereas ICI slightly increased them, and TAM had no effect. To investigate the effect of antiestrogens on breast cancer invasiveness, we generated highly migratory and invasive MCF-7-M5 cells. The migration and invasion of these cells were suppressed by the inhibitor of TGF-β receptor kinase, SB-505124, and estrogen. However, antiestrogens did not suppress the migration and invasion of these cells. In addition, we screened TGF-β target genes whose expression was reduced by estrogen treatment and identified four genes associated with breast cancer invasiveness and poor prognosis. The expression of these genes was not decreased by antiestrogens. These observations provide a new insight into estrogen function and the mechanisms underlying estrogen-mediated suppression of tumor progression.

Original languageEnglish (US)
Pages (from-to)1501-1508
Number of pages8
JournalCancer Science
Volume102
Issue number8
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Transforming Growth Factors
Estrogens
Breast Neoplasms
Estrogen Receptors
Tamoxifen
Cell Movement
Neoplasms
Gene Expression
Growth Factor Receptors
MCF-7 Cells
Phosphotransferases
Neoplasm Metastasis
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-β signaling pathway. / Goto, Natsuka; Hiyoshi, Hiromi; Ito, Ichiaki; Tsuchiya, Mai; Nakajima, Yuka; Yanagisawa, Junn.

In: Cancer Science, Vol. 102, No. 8, 01.08.2011, p. 1501-1508.

Research output: Contribution to journalArticle

Goto, Natsuka ; Hiyoshi, Hiromi ; Ito, Ichiaki ; Tsuchiya, Mai ; Nakajima, Yuka ; Yanagisawa, Junn. / Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-β signaling pathway. In: Cancer Science. 2011 ; Vol. 102, No. 8. pp. 1501-1508.
@article{df0fd8c3f38d43299007471acf1e0036,
title = "Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-β signaling pathway",
abstract = "In the later stages of breast cancer, estrogen receptor (ER)α-negative cancers typically have higher histological grades than ERα-positive cancers, and transforming growth factor (TGF)-β promotes invasion and metastasis. Our previous study indicated that ERα inhibited TGF-β signaling by inducing the degradation of Smad in an estrogen-dependent manner. In the present study, we report that the suppressive effects of ERα and estrogen on tumor progression are mediated by inhibiting TGF-β signaling. Furthermore, we investigated the effects of antiestrogens such as ICI182,780 (ICI) or tamoxifen (TAM) on TGF-β signaling and breast cancer invasiveness. The levels of total Smad and pSmad were reduced by estrogen, whereas ICI slightly increased them, and TAM had no effect. To investigate the effect of antiestrogens on breast cancer invasiveness, we generated highly migratory and invasive MCF-7-M5 cells. The migration and invasion of these cells were suppressed by the inhibitor of TGF-β receptor kinase, SB-505124, and estrogen. However, antiestrogens did not suppress the migration and invasion of these cells. In addition, we screened TGF-β target genes whose expression was reduced by estrogen treatment and identified four genes associated with breast cancer invasiveness and poor prognosis. The expression of these genes was not decreased by antiestrogens. These observations provide a new insight into estrogen function and the mechanisms underlying estrogen-mediated suppression of tumor progression.",
author = "Natsuka Goto and Hiromi Hiyoshi and Ichiaki Ito and Mai Tsuchiya and Yuka Nakajima and Junn Yanagisawa",
year = "2011",
month = "8",
day = "1",
doi = "10.1111/j.1349-7006.2011.01977.x",
language = "English (US)",
volume = "102",
pages = "1501--1508",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-β signaling pathway

AU - Goto, Natsuka

AU - Hiyoshi, Hiromi

AU - Ito, Ichiaki

AU - Tsuchiya, Mai

AU - Nakajima, Yuka

AU - Yanagisawa, Junn

PY - 2011/8/1

Y1 - 2011/8/1

N2 - In the later stages of breast cancer, estrogen receptor (ER)α-negative cancers typically have higher histological grades than ERα-positive cancers, and transforming growth factor (TGF)-β promotes invasion and metastasis. Our previous study indicated that ERα inhibited TGF-β signaling by inducing the degradation of Smad in an estrogen-dependent manner. In the present study, we report that the suppressive effects of ERα and estrogen on tumor progression are mediated by inhibiting TGF-β signaling. Furthermore, we investigated the effects of antiestrogens such as ICI182,780 (ICI) or tamoxifen (TAM) on TGF-β signaling and breast cancer invasiveness. The levels of total Smad and pSmad were reduced by estrogen, whereas ICI slightly increased them, and TAM had no effect. To investigate the effect of antiestrogens on breast cancer invasiveness, we generated highly migratory and invasive MCF-7-M5 cells. The migration and invasion of these cells were suppressed by the inhibitor of TGF-β receptor kinase, SB-505124, and estrogen. However, antiestrogens did not suppress the migration and invasion of these cells. In addition, we screened TGF-β target genes whose expression was reduced by estrogen treatment and identified four genes associated with breast cancer invasiveness and poor prognosis. The expression of these genes was not decreased by antiestrogens. These observations provide a new insight into estrogen function and the mechanisms underlying estrogen-mediated suppression of tumor progression.

AB - In the later stages of breast cancer, estrogen receptor (ER)α-negative cancers typically have higher histological grades than ERα-positive cancers, and transforming growth factor (TGF)-β promotes invasion and metastasis. Our previous study indicated that ERα inhibited TGF-β signaling by inducing the degradation of Smad in an estrogen-dependent manner. In the present study, we report that the suppressive effects of ERα and estrogen on tumor progression are mediated by inhibiting TGF-β signaling. Furthermore, we investigated the effects of antiestrogens such as ICI182,780 (ICI) or tamoxifen (TAM) on TGF-β signaling and breast cancer invasiveness. The levels of total Smad and pSmad were reduced by estrogen, whereas ICI slightly increased them, and TAM had no effect. To investigate the effect of antiestrogens on breast cancer invasiveness, we generated highly migratory and invasive MCF-7-M5 cells. The migration and invasion of these cells were suppressed by the inhibitor of TGF-β receptor kinase, SB-505124, and estrogen. However, antiestrogens did not suppress the migration and invasion of these cells. In addition, we screened TGF-β target genes whose expression was reduced by estrogen treatment and identified four genes associated with breast cancer invasiveness and poor prognosis. The expression of these genes was not decreased by antiestrogens. These observations provide a new insight into estrogen function and the mechanisms underlying estrogen-mediated suppression of tumor progression.

UR - http://www.scopus.com/inward/record.url?scp=79960409619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960409619&partnerID=8YFLogxK

U2 - 10.1111/j.1349-7006.2011.01977.x

DO - 10.1111/j.1349-7006.2011.01977.x

M3 - Article

C2 - 21564419

AN - SCOPUS:79960409619

VL - 102

SP - 1501

EP - 1508

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 8

ER -