A New Culture Model for Enhancing Estrogen Responsiveness in HR+ Breast Cancer Cells through Medium Replacement: Presumed Involvement of Autocrine Factors in Estrogen Resistance

Author:

Jang Seok-Hoon12ORCID,Paek Se Hyun3ORCID,Kim Jong-Kyu3,Seong Je Kyung2ORCID,Lim Woosung1

Affiliation:

1. Department of Surgery, Ewha Womans University Mokdong Hospital, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea

2. Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University, 1, Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea

3. Department of Surgery, Ewha Womans University Seoul Hospital, 260, Gonghang-daero, Gangseo-gu, Seoul 07804, Republic of Korea

Abstract

Hormone receptor-positive breast cancer (HR+ BC) cells depend on estrogen and its receptor, ER. Due to this dependence, endocrine therapy (ET) such as aromatase inhibitor (AI) treatment is now possible. However, ET resistance (ET-R) occurs frequently and is a priority in HR+ BC research. The effects of estrogen have typically been determined under a special culture condition, i.e., phenol red-free media supplemented with dextran-coated charcoal-stripped fetal bovine serum (CS-FBS). However, CS-FBS has some limitations, such as not being fully defined or ordinary. Therefore, we attempted to find new experimental conditions and related mechanisms to improve cellular estrogen responsiveness based on the standard culture medium supplemented with normal FBS and phenol red. The hypothesis of pleiotropic estrogen effects led to the discovery that T47D cells respond well to estrogen under low cell density and medium replacement. These conditions made ET less effective there. The fact that several BC cell culture supernatants reversed these findings implies that housekeeping autocrine factors regulate estrogen and ET responsiveness. Results reproduced in T47D subclone and MCF-7 cells highlight that these phenomena are general among HR+ BC cells. Our findings offer not only new insights into ET-R but also a new experimental model for future ET-R studies.

Funder

Dalim Corporation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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