Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells
IntroductionInsulin-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 t...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-11-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1452981/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849221362746392576 |
|---|---|
| author | Keenan L. Flynn Yan Zheng Janel Y. Sowers Nefretiri J. T. Masangya Kevin D. Houston |
| author_facet | Keenan L. Flynn Yan Zheng Janel Y. Sowers Nefretiri J. T. Masangya Kevin D. Houston |
| author_sort | Keenan L. Flynn |
| collection | DOAJ |
| description | IntroductionInsulin-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.MethodsTo 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, and cells were treated with antiestrogens tamoxifen and fulvestrant. Results and discussionMCF-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. |
| format | Article |
| id | doaj-art-ca609206b5bc4cacb51e299c7cfbd850 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-ca609206b5bc4cacb51e299c7cfbd8502024-11-15T05:10:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-11-011410.3389/fonc.2024.14529811452981Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cellsKeenan L. FlynnYan ZhengJanel Y. SowersNefretiri J. T. MasangyaKevin D. HoustonIntroductionInsulin-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.MethodsTo 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, and cells were treated with antiestrogens tamoxifen and fulvestrant. Results and discussionMCF-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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1452981/fullGPER1Yap/Tazfulvestranttriple negative breast cancerIGFBP-3insulin like growth factor binding protein |
| spellingShingle | Keenan L. Flynn Yan Zheng Janel Y. Sowers Nefretiri J. T. Masangya Kevin D. Houston Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells Frontiers in Oncology GPER1 Yap/Taz fulvestrant triple negative breast cancer IGFBP-3 insulin like growth factor binding protein |
| title | Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells |
| title_full | Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells |
| title_fullStr | Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells |
| title_full_unstemmed | Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells |
| title_short | Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells |
| title_sort | insulin like growth factor binding protein 3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells |
| topic | GPER1 Yap/Taz fulvestrant triple negative breast cancer IGFBP-3 insulin like growth factor binding protein |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1452981/full |
| work_keys_str_mv | AT keenanlflynn insulinlikegrowthfactorbindingprotein3isinducedbytamoxifenandfulvestrantandmodulatesfulvestrantresponseinbreastcancercells AT yanzheng insulinlikegrowthfactorbindingprotein3isinducedbytamoxifenandfulvestrantandmodulatesfulvestrantresponseinbreastcancercells AT janelysowers insulinlikegrowthfactorbindingprotein3isinducedbytamoxifenandfulvestrantandmodulatesfulvestrantresponseinbreastcancercells AT nefretirijtmasangya insulinlikegrowthfactorbindingprotein3isinducedbytamoxifenandfulvestrantandmodulatesfulvestrantresponseinbreastcancercells AT kevindhouston insulinlikegrowthfactorbindingprotein3isinducedbytamoxifenandfulvestrantandmodulatesfulvestrantresponseinbreastcancercells |