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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Breast Cancer
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1452981

The Insulin-like Growth Factor-binding Protein-3 is induced by and modulates the response of breast cancer cells to tamoxifen and fulvestrant

Provisionally accepted
Keenan L. Flynn Keenan L. Flynn 1Yan Zheng Yan Zheng 1,2Janel Y. Sowers Janel Y. Sowers 1Nefretiri Masangya Nefretiri Masangya 1Kevin D. Houston Kevin D. Houston 1*
  • 1 New Mexico State University, Las Cruces, New Mexico, United States
  • 2 University of Texas MD Anderson Cancer Center, Houston, Texas, United States

The final, formatted version of the article will be published soon.

    Insulin-like growth factor binding protein-3 (IGFBP-3) exerts varying effects on estrogen receptor alpha (ERα)-positive and triple-negative breast cancer (TNBC) cells. In ERα-positive cells, IGFBP-3 is antiproliferative and proapoptotic. In contrast, IGFBP-3 stimulates proliferation in triple-negative breast cancer (TNBC) cells via EGFR activation. To identify potential mechanisms that underlie the opposing effects of IGFBP-3 on these two breast cancer subtypes, IGFBP-3 expression was determined in cell line models of both ERα-positive breast cancer and TNBC. MCF-7 and T-47D cells expressed low levels of IGFBP-3 when compared to MDA-MB-231 and MDA-MB-468 cells. MCF-7 cells with acquired resistance to the selective estrogen receptor degrader fulvestrant expressed high IGFBP-3 and MCF-7 cells with constitutive IGFBP-3 expression were fulvestrant resistant. IGFBP-3 expression was increased in all cell lines upon treatment with fulvestrant or the selective estrogen receptor modulator tamoxifen and both fulvestrant and tamoxifen increased TNBC cell proliferation. Further, IGFBP-3 expression was increased by treatment with the GPER1 agonist G-1 and attenuated upon treatment with P17, a YAP/TAZ inhibitor. These data suggest that IGFBP-3 modulates breast cancer cells and is a mediator of breast cancer cell response to fulvestrant and tamoxifen.

    Keywords: GPER11, Yap/Taz2, Fulvestrant3, Triple negative breast cancer4, IGFBP-35, Insulin like growth factor binding protein6

    Received: 21 Jun 2024; Accepted: 15 Oct 2024.

    Copyright: © 2024 Flynn, Zheng, Sowers, Masangya and Houston. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kevin D. Houston, New Mexico State University, Las Cruces, 88003, New Mexico, United States

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