{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:36:06Z","timestamp":1790501766670,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T00:00:00Z","timestamp":1345507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>The treatment of non\u2010localized prostate cancer involves androgen deprivation (AD) therapy which results in tumor regression. Apoptosis has been implicated in the tumor response to AD, but constitutes a small fraction of the total tumor at any time. Cellular senescence is a response to sub\u2010lethal stress in which cells are persistently growth arrested and develop distinct morphological and biochemical characteristics. The occurrence of senescence in prostate tumor tissue after AD therapy has not previously been investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Phenotypic and molecular characteristics of senescence were examined in models of androgen\u2010sensitive prostate cancer after AD and compared with androgen\u2010intact controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In vitro in LNCaP cells, AD induced elevated senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal) staining, decreased proliferation, and increased flow cytometric side scatter while minimally affecting cell viability. The increased expression of the senescence\u2010related proteins Glb1, the cyclin\u2010dependent kinase inhibitor p27\n                      <jats:sup>Kip1<\/jats:sup>\n                      and chromatin\u2010regulating heterochromatin protein 1\u03b3 (HP1\u03b3) were detected in LNCaP cells after AD in vitro by immunoblot and immunofluorescence microscopy. In mice bearing LuCaP xenograft tumors in vivo, surgical castration similarly increased SA\u2010\u03b2\u2010gal staining, increased expression of p27\n                      <jats:sup>Kip1<\/jats:sup>\n                      and HP1\u03b3, and decreased expression of the proliferation marker KI\u201067, with minimal induction of apoptosis identified by detection of cleaved caspase 3 and TUNEL. Immunohistochemical analysis of human prostate tumors removed after AD shows similar induction of Glb1, HP1\u03b3 and decreased KI\u201067.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>We conclude that AD induces characteristics consistent with cellular senescence in androgen\u2010sensitive prostate cancer cells. This finding may explain incomplete tumor regression in response to AD. Prostate 73: 337\u2013345, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.22571","type":"journal-article","created":{"date-parts":[[2012,8,21]],"date-time":"2012-08-21T08:57:23Z","timestamp":1345539443000},"page":"337-345","source":"Crossref","is-referenced-by-count":58,"title":["Androgen deprivation induces senescence characteristics in prostate cancer cells in vitro and in vivo"],"prefix":"10.1002","volume":"73","author":[{"given":"Jonathan A.","family":"Ewald","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Desotelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn 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