Unknown

Dataset Information

0

Estrogen receptors ?1 and ?2 have opposing roles in regulating proliferation and bone metastasis genes in the prostate cancer cell line PC3.


ABSTRACT: The estrogen receptor (ER)?1 is successively lost during cancer progression, whereas its splice variant, ER?2, is expressed in advanced prostate cancer. The latter form of cancer often metastasizes to bone, and we wanted to investigate whether the loss of ER?1 and/or the expression of ER?2 affect such signaling pathways in prostate cancer. Using PC3 and 22Rv1 prostate cancer cell lines that stably express ER?1 or ER?2, we found that the ER? variants differentially regulate genes known to affect tumor behavior. We found that ER?1 repressed the expression of the bone metastasis regulator Runx2 in PC3 cells. By contrast, RUNX2 expression was up-regulated at the mRNA level by ER?2 in PC3 cells, whereas Slug was up-regulated by ER?2 in both PC3 and 22Rv1 cells. In addition, the expression of Twist1, a factor whose expression strongly correlates with high Gleason grade prostate carcinoma, was increased by ER?2. In agreement with the increased Twist1 expression, we found increased expression of Dickkopf homolog 1; Dickkopf homolog 1 is a factor that has been shown to increase the RANK ligand/osteoprotegerin ratio and enhance osteoclastogenesis, indicating that the expression of ER?2 can cause osteolytic cancer. Furthermore, we found that only ER?1 inhibited proliferation, whereas ER?2 increased proliferation. The expression of the proliferation markers Cyclin E, c-Myc, and p45(Skp2) was differentially affected by ER?1 and ER?2 expression. In addition, nuclear ?-catenin protein and its mRNA levels were reduced by ER?1 expression. In conclusion, we found that ER?1 inhibited proliferation and factors known to be involved in bone metastasis, whereas ER?2 increased proliferation and up-regulated factors involved in bone metastasis. Thus, in prostate cancer cells, ER?2 has oncogenic abilities that are in strong contrast to the tumor-suppressing effects of ER?1.

SUBMITTER: Dey P 

PROVIDER: S-EPMC3517717 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Estrogen receptors β1 and β2 have opposing roles in regulating proliferation and bone metastasis genes in the prostate cancer cell line PC3.

Dey Prasenjit P   Jonsson Philip P   Hartman Johan J   Williams Cecilia C   Ström Anders A   Gustafsson Jan-Åke JÅ  

Molecular endocrinology (Baltimore, Md.) 20121001 12


The estrogen receptor (ER)β1 is successively lost during cancer progression, whereas its splice variant, ERβ2, is expressed in advanced prostate cancer. The latter form of cancer often metastasizes to bone, and we wanted to investigate whether the loss of ERβ1 and/or the expression of ERβ2 affect such signaling pathways in prostate cancer. Using PC3 and 22Rv1 prostate cancer cell lines that stably express ERβ1 or ERβ2, we found that the ERβ variants differentially regulate genes known to affect  ...[more]

Similar Datasets

| S-EPMC4150283 | biostudies-literature
| S-EPMC7466142 | biostudies-literature
| S-EPMC4121674 | biostudies-literature
| S-EPMC2791401 | biostudies-literature
| S-EPMC3326570 | biostudies-literature
2024-11-29 | PXD056956 | Pride
| S-EPMC1589996 | biostudies-literature
| S-EPMC4114040 | biostudies-literature
| S-EPMC2262282 | biostudies-literature
| S-EPMC14614 | biostudies-literature