Exposure to EGF and 17 beta-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

• 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 17 beta-estradiol on the proliferation, transformation, expression of markers of stemness, and tumorigenesis of MCF7 human breast adenocarcinoma cells. Exposure to EGF and/or 17 beta-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 beta-estradiol or EGF + 17 beta-estradiol. Immunohistochemistry performed on tumors derived from 17 beta-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 17 beta-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 beta-estradiol altered their responsiveness to short-term stimulatory or inhibitory treatments with EGF, 17 beta-estradiol, transforming growth factor-beta 1 (TGF beta 1), Iressa and SB431542. Therefore, the findings indicated that sustained exposure of MCF7 cells to EGF and/or 17 beta-estradiol resulted in enhanced cell proliferation and mammosphere formation, an increased ratio of CD 44(+)/CD24 cells, and altered responses to short-term treatments with EGF, 17 beta-estradiol, TGF beta 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

epidermal growth factor

17 beta-estradiol

breast cancer

stemness

xenograft

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