Abstract
Androgen deprivation therapy (ADT) is standard frontline therapy for metastatic prostate cancer. However, prostate cancer progresses to a castrate-resistant state. The response of prostate cancer to androgen deprivation is mediated by the androgen receptor (AR). Castrate-resistant disease is marked by a gain-of-function in AR and AR reactivation. The stem cell hypothesis of cancer would therefore predict that AR should be expressed in the prostate cancer stem cell, since genetic selection for gain-of-function changes in AR, such as AR gene amplification, should occur at the level of the stem cell population. Initial reports characterizing prostate cancer stem cells suggest that AR is not expressed in this population, which is an apparent conundrum. Here, we examined the CD44+/24− LNCaP putative stem cell population by in-cell Western and show that AR is expressed at the protein level. Our findings suggest that at least a subset of prostate cancers express AR in the putative stem cell population.
This is a preview of subscription content, log in via an institution to check access.
References
Sharifi N, Gulley JL, Dahut WL (2005) Androgen deprivation therapy for prostate cancer. JAMA 13(294):238–244
Gelmann EP (2002) Molecular biology of the androgen receptor. J Clin Oncol 1(20):3001–3015
Edwards J, Krishna NS, Grigor KM, Bartlett JM (2003) Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer. Br J Cancer 4(89):552–556
Mostaghel EA, Montgomery RB, Lin DW (2007) The basic biochemistry and molecular events of hormone therapy. Curr Urol Rep 8:224–232
Sharifi N, Farrar WL (2006) Androgen receptor as a therapeutic target for androgen independent prostate cancer. Am J Ther 13:166–170
Scher HI, Sawyers CL (2005) Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol 10(23):8253–8261
Stark GR, Debatisse M, Giulotto E, Wahl GM (1989) Recent progress in understanding mechanisms of mammalian DNA amplification. Cell 16(57):901–908
Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 1(65):10946–10951
Patrawala L, Calhoun T, Schneider-Broussard R et al (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 16(25):1696–1708
Sharifi N, Kawasaki BT, Hurt EM, Farrar WL (2006) Stem cells in prostate cancer: resolving the castrate-resistant conundrum and implications for hormonal therapy. Cancer Biol Ther 5:901–906
Hurt EM, Kawasaki BT, Klarmann GK, Farrar WL (2007) Identification and characterization of a putative prostate stem cell population and its differentiated progenitors. Keystone: Stem Cells and Cancer (X2). Keystone, Colorado
Author information
Authors and Affiliations
Corresponding author
Additional information
This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
Rights and permissions
About this article
Cite this article
Sharifi, N., Hurt, E.M. & Farrar, W.L. Androgen receptor expression in prostate cancer stem cells: is there a conundrum?. Cancer Chemother Pharmacol 62, 921–923 (2008). https://doi.org/10.1007/s00280-007-0659-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-007-0659-5