Influence of Estrogen Treatment on ESR1+ and ESR1- Cells in ER+ Breast Cancer : Insights from Single-Cell Analysis of Patient-Derived Xenograft Models
A 100% ER positivity is not required for an endocrine therapy response. Furthermore, while estrogen typically promotes the progression of hormone-dependent breast cancer via the activation of estrogen receptor (ER)-α, estrogen-induced tumor suppression in ER+ breast cancer has been clinically observed. With the success in establishing estrogen-stimulated (SC31) and estrogen-suppressed (GS3) patient-derived xenograft (PDX) models, single-cell RNA sequencing analysis was performed to determine the impact of estrogen on ESR1+ and ESR1- tumor cells. We found that 17β-estradiol (E2)-induced suppression of GS3 transpired through wild-type and unamplified ERα. E2 upregulated the expression of estrogen-dependent genes in both SC31 and GS3; however, E2 induced cell cycle advance in SC31, while it resulted in cell cycle arrest in GS3. Importantly, these gene expression changes occurred in both ESR1+ and ESR1- cells within the same breast tumors, demonstrating for the first time a differential effect of estrogen on ESR1- cells. E2 also upregulated a tumor-suppressor gene, IL-24, in GS3. The apoptosis gene set was upregulated and the G2M checkpoint gene set was downregulated in most IL-24+ cells after E2 treatment. In summary, estrogen affected pathologically defined ER+ tumors differently, influencing both ESR1+ and ESR1- cells. Our results also suggest IL-24 to be a potential marker of estrogen-suppressed tumors.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
|---|---|
| Enthalten in: |
Cancers - 13(2021), 24 vom: 19. Dez. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Mori, Hitomi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Aromatase inhibitor resistance |
|---|
| Anmerkungen: |
Date Revised 29.12.2021 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/cancers13246375 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM334809010 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM334809010 | ||
| 003 | DE-627 | ||
| 005 | 20231225224509.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/cancers13246375 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1115.xml |
| 035 | |a (DE-627)NLM334809010 | ||
| 035 | |a (NLM)34944995 | ||
| 035 | |a (PII)6375 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Mori, Hitomi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Influence of Estrogen Treatment on ESR1+ and ESR1- Cells in ER+ Breast Cancer |b Insights from Single-Cell Analysis of Patient-Derived Xenograft Models |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 29.12.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a A 100% ER positivity is not required for an endocrine therapy response. Furthermore, while estrogen typically promotes the progression of hormone-dependent breast cancer via the activation of estrogen receptor (ER)-α, estrogen-induced tumor suppression in ER+ breast cancer has been clinically observed. With the success in establishing estrogen-stimulated (SC31) and estrogen-suppressed (GS3) patient-derived xenograft (PDX) models, single-cell RNA sequencing analysis was performed to determine the impact of estrogen on ESR1+ and ESR1- tumor cells. We found that 17β-estradiol (E2)-induced suppression of GS3 transpired through wild-type and unamplified ERα. E2 upregulated the expression of estrogen-dependent genes in both SC31 and GS3; however, E2 induced cell cycle advance in SC31, while it resulted in cell cycle arrest in GS3. Importantly, these gene expression changes occurred in both ESR1+ and ESR1- cells within the same breast tumors, demonstrating for the first time a differential effect of estrogen on ESR1- cells. E2 also upregulated a tumor-suppressor gene, IL-24, in GS3. The apoptosis gene set was upregulated and the G2M checkpoint gene set was downregulated in most IL-24+ cells after E2 treatment. In summary, estrogen affected pathologically defined ER+ tumors differently, influencing both ESR1+ and ESR1- cells. Our results also suggest IL-24 to be a potential marker of estrogen-suppressed tumors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ER-positive breast cancer | |
| 650 | 4 | |a ESR1+ and ESR1– cells | |
| 650 | 4 | |a IL-24 | |
| 650 | 4 | |a aromatase inhibitor resistance | |
| 650 | 4 | |a estrogen-induced cell cycle arrest | |
| 650 | 4 | |a patient-derived tumor xenograft | |
| 650 | 4 | |a single-cell RNA sequencing | |
| 700 | 1 | |a Saeki, Kohei |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Gregory |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jinhui |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Hsu, Pei-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Kanaya, Noriko |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Somlo, George |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Masafumi |e verfasserin |4 aut | |
| 700 | 1 | |a Bild, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shiuan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancers |d 2009 |g 13(2021), 24 vom: 19. Dez. |w (DE-627)NLM198667213 |x 2072-6694 |7 nnns |
| 773 | 1 | 8 | |g volume:13 |g year:2021 |g number:24 |g day:19 |g month:12 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cancers13246375 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 13 |j 2021 |e 24 |b 19 |c 12 | ||