Antiproliferative and pro-­apoptotic actions of Estrogen receptor β in prostate cancer

Dey, Prasenjit 1978-

Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer

dc.contributor.advisor	Gustafsson, Jan-Åke
dc.contributor.committeeMember	Ström, Anders M.
dc.contributor.committeeMember	Schwartz, Robert J.
dc.contributor.committeeMember	Webb, Paul
dc.contributor.committeeMember	Wang, Yuhong
dc.creator	Dey, Prasenjit 1978-
dc.date.accessioned	2015-08-16T02:44:14Z
dc.date.available	2015-08-16T02:44:14Z
dc.date.created	May 2013
dc.date.issued	2013-05
dc.date.updated	2015-08-16T02:44:14Z
dc.description.abstract	High Gleason grade prostate cancers are aggressive. Currently, the major target for treatment is the androgen receptor. Recent literature points towards a tumor suppressive role of estrogen receptor β (ERβ), which has a potential to be exploited as a target for novel therapeutics used for treatment of prostate cancer. In Chapter 2 of the thesis, we showed that ERβ-selective agonists elicited an increase in apoptosis and this was accompanied by an increase in expression of the pro-apoptotic factor PUMA. Induction of PUMA was dependent on the presence of the transcription factor FOXO3 but was independent of p53. In the ventral prostates of ERβ-/- mice, expression of FOXO3a is lower than that in WT littermates demonstrating a relationship between ERβ and FOXO3a expression found in PC3 and LNCaP cells. Furthermore, in prostate cancers of Gleason grade 4 or higher there was a marked reduction of both ERβ and FOXO3a, while both genes were well expressed in BPH sections. In Chapter 3 of the thesis, we investigated whether the loss of ERβ (also called as ERβ1) and/or expression of its splice variant ERβ2 affected signaling pathways involved in proliferation and bone metastasis of prostate cancer. We found repressed expression of the bone metastasis regulator Runx2 and its target gene, Slug by ERβ1. In addition, the expression of Twist1, a factor whose expression strongly correlates with high Gleason grade prostate cancer, was increased by ERβ2. In terms of cell cycle modification, of the two receptors, ERβ1, but not ERβ2, inhibited proliferation and expression of the proliferation markers Cyclin E, c-Myc, and p45Skp2. Xenograft studies using athymic nude mice confirmed the proliferative effect of ERβ2, as tumors in mice bearing PC3-ERβ2 cells were substantially larger than tumors in mice bearing PC3-control and PC3-ERβ1 cells.
dc.description.department	Biology and Biochemistry, Department of
dc.format.digitalOrigin	born digital
dc.format.mimetype	application/pdf
dc.identifier.uri	http://hdl.handle.net/10657/955
dc.language.iso	eng
dc.rights	The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subject	Prostate cancer
dc.subject	Estrogen receptor beta
dc.subject	Apoptosis
dc.subject	Proliferation
dc.subject	FOXO3a
dc.subject	PUMA
dc.subject	Bone metastasis
dc.subject.lcsh	Biochemistry
dc.title	Antiproliferative and pro-apoptotic actions of Estrogen receptor β in prostate cancer
dc.type.dcmi	Text
dc.type.genre	Thesis
thesis.degree.college	College of Natural Sciences and Mathematics
thesis.degree.department	Biology and Biochemistry, Department of
thesis.degree.discipline	Biochemistry
thesis.degree.grantor	University of Houston
thesis.degree.level	Doctoral
thesis.degree.name	Doctor of Philosophy