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Prostate progenitor cells proliferate in response to castration.

Abstract：

:Androgen-deprivation is a mainstay of therapy for advanced prostate cancer but tumor regression is usually incomplete and temporary because of androgen-independent cells in the tumor. It has been speculated that these tumor cells resemble the stem/progenitor cells of the normal prostate. The purpose of this study was to examine the response of slow-cycling progenitor cells in the adult mouse prostate to castration. Proliferating cells in the E16 urogenital sinus were pulse labeled by BrdU administration or by doxycycline-controlled labeling of the histone-H2B GFP mouse. A small population of labeled epithelial cells in the adult prostate localized at the junction of the prostatic ducts and urethra. Fluorescence-activated cell sorting (FACS) showed that GFP label-retaining cells were enriched for cells co-expressing stem cell markers Sca-1, CD133, CD44 and CD117 (4- marker cells; 60-fold enrichment). FACS showed, additionally, that 4-marker cells were androgen receptor positive. Castration induced proliferation and dispersal of E16 labeled cells into more distal ductal segments. When naïve adult mice were administered BrdU daily for 2 weeks after castration, 16% of 4-marker cells exhibited BrdU label in contrast to only 6% of all epithelial cells (P<0.01). In sham-castrated controls less than 4% of 4-marker cells were BrdU labeled (P<0.01). The unexpected and admittedly counter-intuitive finding that castration induced progenitor cell proliferation suggests that androgen deprivation therapy in men with advanced prostate cancer could not only exert pleiotrophic effects on tumor sub-populations but may induce inadvertent expansion of tumor stem cells.

journal_name

Stem Cell Res

journal_title

Stem cell research

authors

Shi X,Gipp J,Dries M,Bushman W

doi

10.1016/j.scr.2014.04.005

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

154-63

issue

1

eissn

1873-5061

issn

1876-7753

pii

S1873-5061(14)00041-5

journal_volume

13

pub_type

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