Tumour-suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model
(2020) In Journal of Pathology 251(3). p.297-309- Abstract
- Oestrogen receptor β (ERβ) has been suggested to have anti-proliferative and anti-tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour-promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorectal cancer (CRC) patients. Herein, we investigated the possible anti-tumour effect of ERβ and its selective agonist. CRC patients with high ERβ expression had significantly higher levels of membrane-associated β-catenin, cysteinyl leukotriene receptor 2 (CysLT2 R) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which have anti-tumour effects,... (More)
- Oestrogen receptor β (ERβ) has been suggested to have anti-proliferative and anti-tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour-promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorectal cancer (CRC) patients. Herein, we investigated the possible anti-tumour effect of ERβ and its selective agonist. CRC patients with high ERβ expression had significantly higher levels of membrane-associated β-catenin, cysteinyl leukotriene receptor 2 (CysLT2 R) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which have anti-tumour effects, but lower levels of nuclear β-catenin, cysteinyl leukotriene receptor 1 (CysLT1 R) and cyclooxygenase-2 (COX-2), which have tumour-promoting effects. These interesting findings were further supported by two different publicly available CRC mRNA datasets that showed a significant positive correlation between ERβ expression and 15-PGDH and CysLT2 R expression and a negative correlation between ERβ expression and β-catenin, CysLT1 R and COX-2 expression. We next evaluated ERβ expression in three different colon cancer mouse models; ERβ expression was negatively correlated with tumorigenesis. Furthermore, treatment with the ERβ-agonist ERB-041 reduced CysLT1 R, active β-catenin and COX-2 levels but increased phospho-β-catenin, CysLT2 R and 15-PGDH levels in HCT-116, Caco-2 and SW-480 colon cancer cells compared to vehicle-treated cells. Interestingly, ERB-041-treated cells showed significantly decreased migration, survival, and colonosphere formation and increased apoptotic activity, as indicated by increased CASPASE-3 and apoptotic blebs. Finally, patients with low ERβ expression had significantly more distant metastasis at the time of diagnosis than patients with high ERβ expression. Therefore, we studied the effects of ERB-041-treated colon cancer cells in a zebrafish xenograft model. We found significantly less distant metastasis of ERB-041-treated cells compared to vehicle-treated cells. These results further support ERβ's anti-tumour role in colorectal cancer and the possible use of its agonist in CRC patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/879f281a-f903-4928-9fff-fda6c6057e52
- author
- Topi, Geriolda LU ; Ranjan Satapathy, Shakti LU ; Dash, Pujarini LU ; Mehrabi, Syrina LU ; Ehrnström, Roy LU ; Olsson, Roger LU ; Lydrup, Marie-Louise LU and Sjölander, Anita LU
- organization
-
- LUCC: Lund University Cancer Centre
- Cell Pathology, Malmö (research group)
- Pathology, Malmö (research group)
- NanoLund: Centre for Nanoscience
- Centre for Analysis and Synthesis
- Chemical Biology and Therapeutics (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Surgery (research group)
- publishing date
- 2020-07
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Pathology
- volume
- 251
- issue
- 3
- pages
- 13 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:32333795
- scopus:85084587126
- ISSN
- 0022-3417
- DOI
- 10.1002/path.5453
- language
- English
- LU publication?
- yes
- id
- 879f281a-f903-4928-9fff-fda6c6057e52
- date added to LUP
- 2020-05-04 21:07:31
- date last changed
- 2023-11-20 04:06:50
@article{879f281a-f903-4928-9fff-fda6c6057e52, abstract = {{Oestrogen receptor β (ERβ) has been suggested to have anti-proliferative and anti-tumour effects in breast and prostate cancer cells, but other studies have indicated its tumour-promoting effects. Understanding the complex effects of this receptor in different contexts requires further study. We reported that high ERβ expression is independently associated with improved prognosis in female colorectal cancer (CRC) patients. Herein, we investigated the possible anti-tumour effect of ERβ and its selective agonist. CRC patients with high ERβ expression had significantly higher levels of membrane-associated β-catenin, cysteinyl leukotriene receptor 2 (CysLT2 R) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which have anti-tumour effects, but lower levels of nuclear β-catenin, cysteinyl leukotriene receptor 1 (CysLT1 R) and cyclooxygenase-2 (COX-2), which have tumour-promoting effects. These interesting findings were further supported by two different publicly available CRC mRNA datasets that showed a significant positive correlation between ERβ expression and 15-PGDH and CysLT2 R expression and a negative correlation between ERβ expression and β-catenin, CysLT1 R and COX-2 expression. We next evaluated ERβ expression in three different colon cancer mouse models; ERβ expression was negatively correlated with tumorigenesis. Furthermore, treatment with the ERβ-agonist ERB-041 reduced CysLT1 R, active β-catenin and COX-2 levels but increased phospho-β-catenin, CysLT2 R and 15-PGDH levels in HCT-116, Caco-2 and SW-480 colon cancer cells compared to vehicle-treated cells. Interestingly, ERB-041-treated cells showed significantly decreased migration, survival, and colonosphere formation and increased apoptotic activity, as indicated by increased CASPASE-3 and apoptotic blebs. Finally, patients with low ERβ expression had significantly more distant metastasis at the time of diagnosis than patients with high ERβ expression. Therefore, we studied the effects of ERB-041-treated colon cancer cells in a zebrafish xenograft model. We found significantly less distant metastasis of ERB-041-treated cells compared to vehicle-treated cells. These results further support ERβ's anti-tumour role in colorectal cancer and the possible use of its agonist in CRC patients.}}, author = {{Topi, Geriolda and Ranjan Satapathy, Shakti and Dash, Pujarini and Mehrabi, Syrina and Ehrnström, Roy and Olsson, Roger and Lydrup, Marie-Louise and Sjölander, Anita}}, issn = {{0022-3417}}, language = {{eng}}, number = {{3}}, pages = {{297--309}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Journal of Pathology}}, title = {{Tumour-suppressive effect of oestrogen receptor β in colorectal cancer patients, colon cancer cells, and a zebrafish model}}, url = {{http://dx.doi.org/10.1002/path.5453}}, doi = {{10.1002/path.5453}}, volume = {{251}}, year = {{2020}}, }