Exposure to EGF and 17β‑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

Cunha,Sara I.; Jia,Min; Souchelnytskyi,Serhiy

doi:10.3892/ijmm.2018.3737

Exposure to EGF and 17β‑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

Authors:
- Sara I. Cunha
- Min Jia
- Serhiy Souchelnytskyi
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Affiliations: Department of Immunology, Genetics and Pathology, Uppsala University, 75237 Uppsala, Sweden, Department of Biosciences and Nutrition, Karolinska Institutet, 14157 Stockholm, Sweden, College of Medicine, Qatar University, Doha 2713, Qatar
Published online on: June 20, 2018 https://doi.org/10.3892/ijmm.2018.3737
Pages: 1615-1624

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Abstract

Epidermal 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 17β‑estradiol on the proliferation, transformation, expression of markers of stemness, and tumorigenesis of MCF7 human breast adenocarcinoma cells. Exposure to EGF and/or 17β‑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, 17β‑estradiol or EGF + 17β‑estradiol. Immunohistochemistry performed on tumors derived from 17β‑estradiol‑exposed cells revealed reduced cell proliferation and vessel scores, according to the results obtained using Ki67 and von Willebrand factor staining, respectively. The EGF‑ and/or 17β‑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 17β‑estradiol altered their responsiveness to short‑term stimulatory or inhibitory treatments with EGF, 17β‑estradiol, transforming growth factor‑β1 (TGFβ1), Iressa and SB431542. Therefore, the findings indicated that sustained exposure of MCF7 cells to EGF and/or 17β‑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, 17β‑estradiol, TGFβ1, and drugs inhibiting these signaling pathways. However, this sustained exposure was not sufficient to affect tumor take or volume in a xenograft mouse model.

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