Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.

Sequential treatment with endocrine or chemotherapy is generally used in the treatment of estrogen receptor (ER)-positive recurrent breast cancer. To date, few studies have investigated the effect of long-term endocrine therapy on the response to subsequent chemotherapy in ER-positive breast cancer....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Takayuki Watanabe, Takaaki Oba, Keiji Tanimoto, Tomohiro Shibata, Shinobu Kamijo, Ken-Ichi Ito
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5362605a848c460bb25cd70fbbc06aa8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5362605a848c460bb25cd70fbbc06aa8
record_format	dspace
spelling	oai:doaj.org-article:5362605a848c460bb25cd70fbbc06aa82021-12-02T20:10:59ZTamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.1932-620310.1371/journal.pone.0252822https://doaj.org/article/5362605a848c460bb25cd70fbbc06aa82021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252822https://doaj.org/toc/1932-6203Sequential treatment with endocrine or chemotherapy is generally used in the treatment of estrogen receptor (ER)-positive recurrent breast cancer. To date, few studies have investigated the effect of long-term endocrine therapy on the response to subsequent chemotherapy in ER-positive breast cancer. We examined whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER-positive breast cancer cells. Three ER-positive breast cancer cell lines (T47D, MCF7, BT474) and tamoxifen-resistant sublines (T47D/T, MCF7/T, BT474/T) were analyzed for sensitivity to 5-fluorouracil, paclitaxel, and doxorubicin. The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. MCF7/T cells became more sensitive to 5-fluorouracil than wild-type (wt)-MCF7 cells. In addition, the apoptosis induced by 5-fluorouracil was significantly increased in MCF7/T cells. However, no difference in sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T cells compared with their wt cells. Dihydropyrimidine dehydrogenase (DPYD) mRNA expression was significantly decreased in MCF7/T cells compared with wt-MCF7 cells. The expression of DPYD mRNA was restored with 5-azacytidine treatment in MCF7/T cells. In addition, DPYD 3'-UTR luciferase activity was significantly reduced in MCF7/T cells. These data indicated that the expression of DPYD mRNA was repressed by methylation of the DPYD promoter region and post-transcriptional regulation by miRNA in MCF7/T cells. In the mouse xenograft model, capecitabine significantly reduced the tumor volume in MCF7/T compared with MCF7. The results of this study indicate that endocrine therapy could alter the sensitivity to chemotherapeutic agents in a subset of breast cancers, and 5-fluorouracil may be effective in tamoxifen-resistant breast cancers.Takayuki WatanabeTakaaki ObaKeiji TanimotoTomohiro ShibataShinobu KamijoKen-Ichi ItoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252822 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takayuki Watanabe Takaaki Oba Keiji Tanimoto Tomohiro Shibata Shinobu Kamijo Ken-Ichi Ito Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
description	Sequential treatment with endocrine or chemotherapy is generally used in the treatment of estrogen receptor (ER)-positive recurrent breast cancer. To date, few studies have investigated the effect of long-term endocrine therapy on the response to subsequent chemotherapy in ER-positive breast cancer. We examined whether a preceding endocrine therapy affects the sensitivity to subsequent chemotherapy in ER-positive breast cancer cells. Three ER-positive breast cancer cell lines (T47D, MCF7, BT474) and tamoxifen-resistant sublines (T47D/T, MCF7/T, BT474/T) were analyzed for sensitivity to 5-fluorouracil, paclitaxel, and doxorubicin. The mRNA levels of factors related to drug sensitivity were analyzed by RT-PCR. MCF7/T cells became more sensitive to 5-fluorouracil than wild-type (wt)-MCF7 cells. In addition, the apoptosis induced by 5-fluorouracil was significantly increased in MCF7/T cells. However, no difference in sensitivity to chemotherapeutic agents was observed in T47D/T and BT474/T cells compared with their wt cells. Dihydropyrimidine dehydrogenase (DPYD) mRNA expression was significantly decreased in MCF7/T cells compared with wt-MCF7 cells. The expression of DPYD mRNA was restored with 5-azacytidine treatment in MCF7/T cells. In addition, DPYD 3'-UTR luciferase activity was significantly reduced in MCF7/T cells. These data indicated that the expression of DPYD mRNA was repressed by methylation of the DPYD promoter region and post-transcriptional regulation by miRNA in MCF7/T cells. In the mouse xenograft model, capecitabine significantly reduced the tumor volume in MCF7/T compared with MCF7. The results of this study indicate that endocrine therapy could alter the sensitivity to chemotherapeutic agents in a subset of breast cancers, and 5-fluorouracil may be effective in tamoxifen-resistant breast cancers.
format	article
author	Takayuki Watanabe Takaaki Oba Keiji Tanimoto Tomohiro Shibata Shinobu Kamijo Ken-Ichi Ito
author_facet	Takayuki Watanabe Takaaki Oba Keiji Tanimoto Tomohiro Shibata Shinobu Kamijo Ken-Ichi Ito
author_sort	Takayuki Watanabe
title	Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
title_short	Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
title_full	Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
title_fullStr	Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
title_full_unstemmed	Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
title_sort	tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5362605a848c460bb25cd70fbbc06aa8
work_keys_str_mv	AT takayukiwatanabe tamoxifenresistancealterssensitivityto5fluorouracilinasubsetofestrogenreceptorpositivebreastcancer AT takaakioba tamoxifenresistancealterssensitivityto5fluorouracilinasubsetofestrogenreceptorpositivebreastcancer AT keijitanimoto tamoxifenresistancealterssensitivityto5fluorouracilinasubsetofestrogenreceptorpositivebreastcancer AT tomohiroshibata tamoxifenresistancealterssensitivityto5fluorouracilinasubsetofestrogenreceptorpositivebreastcancer AT shinobukamijo tamoxifenresistancealterssensitivityto5fluorouracilinasubsetofestrogenreceptorpositivebreastcancer AT kenichiito tamoxifenresistancealterssensitivityto5fluorouracilinasubsetofestrogenreceptorpositivebreastcancer
_version_	1718374945647493120

Tamoxifen resistance alters sensitivity to 5-fluorouracil in a subset of estrogen receptor-positive breast cancer.

Ejemplares similares