NDLI: Androgen Deprivation-Induced Senescence Promotes Outgrowth of Androgen-Refractory Prostate Cancer Cells

Content Provider	PubMed Central
Author	Burton, Dominick G. A. Giribaldi, Maria G. Munoz, Anisleidys Halvorsen, Katherine Patel, Asmita Jorda, Merce Carlos, Perez-stable Rai, Priyamvada
Editor	Agoulnik, Irina U.
Copyright Year	2013
Abstract	Androgen deprivation (AD) is an effective method for initially suppressing prostate cancer (PC) progression. However, androgen-refractory PC cells inevitably emerge from the androgen-responsive tumor, leading to incurable disease. Recent studies have shown AD induces cellular senescence, a phenomenon that is cell-autonomously tumor-suppressive but which confers tumor-promoting adaptations that can facilitate the advent of senescence-resistant malignant cell populations. Because androgen-refractory PC cells emerge clonally from the originally androgen-responsive tumor, we sought to investigate whether AD-induced senescence (ADIS) affects acquisition of androgen-refractory behavior in androgen-responsive LNCaP and LAPC4 prostate cancer cells. We find that repeated exposure of these androgen-responsive cells to senescence-inducing stimuli via cyclic AD leads to the rapid emergence of ADIS-resistant, androgen-refractory cells from the bulk senescent cell population. Our results show that the ADIS phenotype is associated with tumor-promoting traits, notably chemoresistance and enhanced pro-survival mechanisms such as inhibition of p53-mediated cell death, which encourage persistence of the senescent cells. We further find that pharmacologic enforcement of p53/Bax activation via Nutlin-3 prior to establishment of ADIS is required to overcome the associated pro-survival response and preferentially trigger pervasive cell death instead of senescence during AD. Thus our study demonstrates that ADIS promotes outgrowth of androgen-refractory PC cells and is consequently a suboptimal tumor-suppressor response to AD.
Related Links	http://dx.doi.org/10.1371/journal.pone.0068003
Starting Page	68003
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	6
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-06-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

ARv7 promotes the escape of prostate cancer cells from androgen deprivation therapy-induced senescence by mediating the SKP2/p27 axis

Inactivation of ATM/ATR DNA Damage Checkpoint Promotes Androgen Induced Chromosomal Instability in Prostate Epithelial Cells

Effects of Androgen Deprivation on Cerebral Morphometry in Prostate Cancer Patients – An Exploratory Study

CCAAT/Enhancer Binding Protein β Controls Androgen Deprivation-Induced Senescence in Prostate Cancer Cells

Androgen Receptor Promotes Ligand-Independent Prostate Cancer Progression through c-Myc Upregulation

Transcription Factors Involved in Prostate Gland Adaptation to Androgen Deprivation

Sox2 Is an Androgen Receptor-Repressed Gene That Promotes Castration-Resistant Prostate Cancer

TPL2/COT/MAP3K8 (TPL2) Activation Promotes Androgen Depletion-Independent (ADI) Prostate Cancer Growth

Androgen-Regulated Transcriptional Control of Sialyltransferases in Prostate Cancer Cells

Androgen Deprivation-Induced Senescence Promotes Outgrowth of Androgen-Refractory Prostate Cancer Cells

Similar Documents

ARv7 promotes the escape of prostate cancer cells from androgen deprivation therapy-induced senescence by mediating the SKP2/p27 axis

Inactivation of ATM/ATR DNA Damage Checkpoint Promotes Androgen Induced Chromosomal Instability in Prostate Epithelial Cells

Effects of Androgen Deprivation on Cerebral Morphometry in Prostate Cancer Patients – An Exploratory Study

CCAAT/Enhancer Binding Protein β Controls Androgen Deprivation-Induced Senescence in Prostate Cancer Cells

Androgen Receptor Promotes Ligand-Independent Prostate Cancer Progression through c-Myc Upregulation

Transcription Factors Involved in Prostate Gland Adaptation to Androgen Deprivation

Sox2 Is an Androgen Receptor-Repressed Gene That Promotes Castration-Resistant Prostate Cancer

TPL2/COT/MAP3K8 (TPL2) Activation Promotes Androgen Depletion-Independent (ADI) Prostate Cancer Growth

Androgen-Regulated Transcriptional Control of Sialyltransferases in Prostate Cancer Cells

Androgen Deprivation-Induced Senescence Promotes Outgrowth of Androgen-Refractory Prostate Cancer Cells