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AuthorCunha S.I.
AuthorJia M.
AuthorSouchelnytskyi S.
Available date2020-03-03T06:19:35Z
Publication Date2018
Publication NameInternational Journal of Molecular Medicine
ISSN11073756
URIhttp://dx.doi.org/10.3892/ijmm.2018.3737
URIhttp://hdl.handle.net/10576/13194
AbstractEpidermal growth factor (EGF) and estrogen are potent regulators of breast tumorigenesis. Their short-term actions on human breast epithelial cells have been investigated extensively. However, the consequence of a long-term exposure to EGF and estrogen remains to be fully elucidated. The present study examined the effects of long-term exposure to EGF and 17?-estradiol on the proliferation, transformation, expression of markers of stemness, and tumorigenesis of McF7 human breast adenocarcinoma cells. Exposure to EGF and/or 17?-estradiol irreversibly enhanced the proliferation rate of McF7 cells, even following withdrawal. However, in a mouse xenograft experiment, no significant difference in tumor volume was observed between tumors derived from cells exposed to EGF, 17?-estradiol or EGF + 17?-estradiol. Immunohistochemistry performed on tumors derived from 17?-estradiol-exposed cells revealed reduced cell proliferation and vessel scores, according to the results obtained using Ki67 and von Willebrand factor staining, respectively. The EGFand/or 17?-estradiol-treated cells exhibited an increased ratio of cluster of differentiation (cd)44+/cd24 cells and enhanced ability to form mammospheres. Furthermore, the long-term exposure of McF7 cells to EGF and 17?-estradiol altered their responsiveness to short-term stimulatory or inhibitory treatments with EGF, 17?-estradiol, transforming growth factor-?1 (TGF?1), Iressa and SB431542. Therefore, the findings indicated that sustained exposure of McF7 cells to EGF and/or 17?-estradiol resulted in enhanced cell proliferation and mammosphere formation, an increased ratio of cd44+/cd24 cells, and altered responses to short-term treatments with EGF, 17?-estradiol, TGF?1, and drugs inhibiting these signaling pathways. However, this sustained exposure was not sufficient to affect tumor take or volume in a xenograft mouse model.
SponsorThis study was supported in part by grants from the Swedish Institute, the EU program RTN EpiPlastcarcinoma and Erasmus KI-UWM (grant nos. QUST-SPR-2017-12, QUST-SPR-2017-11, NPRP9-453-3-089, HMc-MRc-RP16354 and HMc-MRc-RP-iTRI to SS).
Languageen
PublisherSpandidos Publications
dc.source Scopus
Subject17-estradiol
SubjectBreast cancer
SubjectEpidermal growth factor
SubjectStemness
SubjectXenograft
TitleExposure to EGF and 17-estradiol irreversibly affects the proliferation and transformation of MCF7 cells but is not sufficient to promote tumor growth in a xenograft mouse model upon withdrawal of exposure
TypeArticle
Pagination1615 - 1624
Issue Number3
Volume Number42


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