Variability in the androgen response of prostate epithelium to 5alpha-reductase inhibition: implications for prostate cancer chemoprevention.

Abstract:

:Inhibitors of 5alpha-reductase (SRD5A) that lower intraprostatic levels of dihydrotestosterone (DHT) reduce the overall incidence of prostate cancer (PCa), but there is significant variation in chemopreventive activity between individual men. In seeking molecular alterations that might underlie this variation, we compared gene expression patterns in patients with localized PCa who were randomized to prostatectomy alone versus treatment with two different doses of the SRD5A inhibitor dutasteride. Prostatic levels of DHT were decreased by >90% in both dutasteride-treated patient groups versus the untreated patient group. Despite significant and uniform suppression of tissue DHT, unsupervised clustering based on prostatic gene expression did not discriminate these groups. However, subjects could be resolved into distinct cohorts characterized by high or low expression of genes regulated by the androgen receptor (AR), based solely on AR transcript expression. The higher-dose dutasteride treatment group was found to include significantly fewer cancers with TMPRSS2-ERG genetic fusions. Dutasteride treatment was associated with highly variable alterations in benign epithelial gene expression. Segregating subjects based on expression of AR and androgen-regulated genes revealed that patients are differentially sensitive to SRD5A inhibition. Our findings suggest that AR levels may predict the chemopreventive efficacy of SRD5A inhibitors.

journal_name

Cancer Res

journal_title

Cancer research

authors

Mostaghel EA,Geng L,Holcomb I,Coleman IM,Lucas J,True LD,Nelson PS

doi

10.1158/0008-5472.CAN-09-2509

subject

Has Abstract

pub_date

2010-02-15 00:00:00

pages

1286-95

issue

4

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-09-2509

journal_volume

70

pub_type

杂志文章
  • A tetravalent single-chain antibody-streptavidin fusion protein for pretargeted lymphoma therapy.

    abstract::Single-chain Fv antibody fragments from the CD20-specific murine monoclonal antibody B9E9 were genetically engineered as streptavidin fusions [single-chain Fv-streptavidin (scFvSA) fusion protein] for use in pretargeted radioimmunotherapy. The scFvSA constructs were expressed as soluble, tetrameric species in the peri...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Schultz J,Lin Y,Sanderson J,Zuo Y,Stone D,Mallett R,Wilbert S,Axworthy D

    更新日期:2000-12-01 00:00:00

  • Tamoxifen DNA damage detected in human endometrium using accelerator mass spectrometry.

    abstract::This study was aimed to establish whether tamoxifen binds irreversibly to uterine DNA when given to women. Patients were given a single therapeutic dose of [(14)C]tamoxifen citrate orally (20 mg, 0.37 or 1.85 MBq) approximately 18 h prior to hysterectomy or breast surgery. Nonmalignant uterine tissue was separated int...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Martin EA,Brown K,Gaskell M,Al-Azzawi F,Garner RC,Boocock DJ,Mattock E,Pring DW,Dingley K,Turteltaub KW,Smith LL,White IN

    更新日期:2003-12-01 00:00:00

  • Isolation and characterization of subclones of L1210 murine leukemia with different sensitivities to various cytotoxic agents.

    abstract::Two subclones of L1210 murine leukemia (L1210-46.1 and L1210-56.3) were isolated in the absence of selective agents. Subclone 56.3 appeared to be more sensitive than was subclone 46.1 to treatment with dexamethasone, 1-beta-D-arabinofuranosyl cytosine, vincristine, and X-irradiation. No differences between the parent ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Brouwer M,Smets LA,Jongsma AP

    更新日期:1983-06-01 00:00:00

  • Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection.

    abstract::Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-0669

    authors: Erkanli A,Taylor DD,Dean D,Eksir F,Egger D,Geyer J,Nelson BH,Stone B,Fritsche HA,Roden RB

    更新日期:2006-02-01 00:00:00

  • Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with Abelson murine leukemia virus and recombinant SV40 retrovirus.

    abstract::Mouse C1 line cells are megakaryoblastic cells established by coinfection of Abelson murine leukemia virus and recombinant simian virus 40. We examined the effects of various compounds on growth and differentiation of these cells. Megakaryocytic differentiation of C1 cells was not induced by cytokines that stimulate m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Honma Y,Okabe-Kado J,Kasukabe T,Hozumi M,Kajigaya S,Suda T,Miura Y

    更新日期:1991-09-01 00:00:00

  • Ductal access for prevention and therapy of mammary tumors.

    abstract::In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraduc...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-4329

    authors: Murata S,Kominsky SL,Vali M,Zhang Z,Garrett-Mayer E,Korz D,Huso D,Baker SD,Barber J,Jaffee E,Reilly RT,Sukumar S

    更新日期:2006-01-15 00:00:00

  • PAK1 tyrosine phosphorylation is required to induce epithelial-mesenchymal transition and radioresistance in lung cancer cells.

    abstract::The p21-activated Ser/Thr kinase 1 (PAK1) kinase has an essential role in tumorigenesis and cell survival in many cancers, but its regulation is not fully understood. In this study, we showed that in response to irradiation of lung cancer cells, PAK1 was upregulated, tyrosine phosphorylated, and translocated to the nu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-0735

    authors: Kim E,Youn H,Kwon T,Son B,Kang J,Yang HJ,Seong KM,Kim W,Youn B

    更新日期:2014-10-01 00:00:00

  • Importance of epidermal growth factor in implantation and growth of mouse mammary tumor in female nude mice.

    abstract::In female nude mice, epidermal growth factor (EGF) was present at a mean concentration of 42.8 +/- 16.9 (SD) ng/mg wet tissue in the submandibular gland and 0.28 +/- 0.13 ng/ml in the plasma. Sialoadenectomy (removal of the submandibular glands) decreased circulating EGF to undetectable levels (less than 0.1 ng/ml). T...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Tsutsumi O,Tsutsumi A,Oka T

    更新日期:1987-09-01 00:00:00

  • Perivascular cells harboring multiple endocrine neoplasia type 1 alterations are neoplastic cells in angiofibromas.

    abstract::Although neoplasia is caused by clonal proliferation of cells, the resulting tumors are frequently heterogeneous, being composed of both neoplastic and reactive cells. Therefore, identification of tumors as neoplastic processes is frequently obscured. We studied cutaneous angiofibroma, which is a tumor of unknown etio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Vortmeyer AO,Böni R,Pack SD,Darling TN,Zhuang Z

    更新日期:1999-01-15 00:00:00

  • Inhibition of miR-328-3p Impairs Cancer Stem Cell Function and Prevents Metastasis in Ovarian Cancer.

    abstract::Cancer stem cells (CSC) play a central role in cancer metastasis and development of drug resistance. miRNA are important in regulating CSC properties and are considered potential therapeutic targets. Here we report that miR-328-3p (miR-328) is significantly upregulated in ovarian CSC. High expression of miR-328 mainta...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-18-3668

    authors: Srivastava AK,Banerjee A,Cui T,Han C,Cai S,Liu L,Wu D,Cui R,Li Z,Zhang X,Xie G,Selvendiran K,Patnaik S,Karpf AR,Liu J,Cohn DE,Wang QE

    更新日期:2019-05-01 00:00:00

  • Plasminogen activators and tumor development in the human colon: activity levels in normal mucosa, adenomatous polyps, and adenocarcinomas.

    abstract::Malignant changes are often accompanied by alterations in activity and composition of the plasminogen activators (PA). To study the relationship between PA expression and the development of colorectal cancer, we determined urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) activit...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: de Bruin PA,Griffioen G,Verspaget HW,Verheijen JH,Lamers CB

    更新日期:1987-09-01 00:00:00

  • Maleic vinyl ether activation of murine macrophages against lung-metastasizing tumors.

    abstract::A 16,500 molecular weight fraction of maleic vinyl ether (MVE-2) induced tumoristatic and tumoricidal activity in peritoneal macrophages of BALB/c and C57BL/6 mice following i.p. administration. Growth of B16 melanoma cells in vitro was inhibited up to 85% by MVE-2-activated, but not resident, peritoneal macrophages. ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Loveless SE,Munson AE

    更新日期:1981-10-01 00:00:00

  • Prognostic value and function of KLF4 in prostate cancer: RNAa and vector-mediated overexpression identify KLF4 as an inhibitor of tumor cell growth and migration.

    abstract::KLF4/GLKF4 is a transcription factor that can have divergent functions in different malignancies. The role of KLF4 in prostate cancer etiology remains unclear. We have recently reported that small double-stranded RNA can induce gene expression by targeting promoter sequence in a phenomenon referred to as RNA activatio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2414

    authors: Wang J,Place RF,Huang V,Wang X,Noonan EJ,Magyar CE,Huang J,Li LC

    更新日期:2010-12-15 00:00:00

  • The diet, nutrition, and cancer program of the NCI National Cancer Program.

    abstract::In November 1974, in response to a mandate in the revised National Cancer Act of 1974, a plan was introduced for the formation of a Diet, Nutrition, and Cancer Program. Dr. Frank J. Rauscher, Director of the National Cancer Institute, selected a group of scientists who defined the goals of the program and recommended ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gori GB

    更新日期:1975-11-01 00:00:00

  • Cross-linkage of nucleophosmin in tumor cells by nitrogen mustard.

    abstract::Mouse leukemia (P388) cells were incubated in cell culture medium containing nitrogen mustard [2-chloro-N-(2-chloroethyl)-N-methylethanamine] for 4 h. The nucleophosmin immunoband with a molecular weight of 37,000 (p37; other molecular weights are similarly designated) was observed in both control and nitrogen mustard...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chan PK

    更新日期:1989-06-15 00:00:00

  • A recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma results in replacement of the 5' regulatory region of BCL6 with a novel H4 histone gene.

    abstract::3q27 translocations affecting the BCL6 gene can involve not only immunoglobulin genes (IG) but also other as yet uncharacterized chromosomal loci as partners. Here, we describe cloning of the junctional area of a recurring translocation, t(3;6)(q27;p21), in non-Hodgkin's lymphoma of B-cell type and isolation of clones...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Akasaka T,Miura I,Takahashi N,Akasaka H,Yonetani N,Ohno H,Fukuhara S,Okuma M

    更新日期:1997-01-01 00:00:00

  • MAFB Promotes Cancer Stemness and Tumorigenesis in Osteosarcoma through a Sox9-Mediated Positive Feedback Loop.

    abstract::Despite the fact that osteosarcoma is one of the most common primary bone malignancies with poor prognosis, the mechanism behind the pathogenesis of osteosarcoma is only partially known. Here we characterized differentially expressed genes by extensive analysis of several publicly available gene expression profile dat...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-1764

    authors: Chen Y,Wang T,Huang M,Liu Q,Hu C,Wang B,Han D,Chen C,Zhang J,Li Z,Liu C,Lei W,Chang Y,Wu M,Xiang D,Chen Y,Wang R,Huang W,Lei Z,Chu X

    更新日期:2020-06-15 00:00:00

  • Interaction between the protein kinase B-Raf and the alpha-subunit of the 11S proteasome regulator.

    abstract::Protein kinases of the Raf family act as signal-transducing elements downstream of activated cell surface receptors and are involved in the regulation of proliferation, differentiation, and cell survival. Whereas the role of c-Raf-1 as a mitogen-activated protein/extracellular signal-regulated kinase activator within ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kalmes A,Hagemann C,Weber CK,Wixler L,Schuster T,Rapp UR

    更新日期:1998-07-15 00:00:00

  • Vascular endothelial growth factor is a predictor of relapse and stage progression in superficial bladder cancer.

    abstract::Tumor development is angiogenesis dependent, and vascular endothelial growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficial bladder cancers was associated with earlier recurrence (P = 0.001; hazard ratio, 3.09) and progression to a more invasive...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Crew JP,O'Brien T,Bradburn M,Fuggle S,Bicknell R,Cranston D,Harris AL

    更新日期:1997-12-01 00:00:00

  • Identification of hypoxia-regulated proteins in head and neck cancer by proteomic and tissue array profiling.

    abstract::Hypoxia within solid tumors decreases therapeutic efficacy, and identification of hypoxia markers may influence the choice of therapeutic modality. Here, we used a proteomic approach to identify hypoxia-regulated proteins and validated their use as endogenous indicators of tumor hypoxia. Using two-dimensional gel elec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-0899

    authors: Chen Y,Shi G,Xia W,Kong C,Zhao S,Gaw AF,Chen EY,Yang GP,Giaccia AJ,Le QT,Koong AC

    更新日期:2004-10-15 00:00:00

  • Dietary iodine deficiency as a tumor promoter and carcinogen in male F344/NCr rats.

    abstract::Groups of 6-wk-old male F344/NCr rats received a single i.v. injection of either vehicle or N-nitrosomethylurea (Cas: 684-93-5) (MNU) at a dose of 41.2 mg/kg body weight. Two wk later, groups of rats were placed on iodine-deficient, iodine-adequate, or commercial (Wayne Lab Blox) diets, or one of these diets and witho...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ohshima M,Ward JM

    更新日期:1986-02-01 00:00:00

  • An exponential-Gompertzian description of LoVo cell tumor growth from in vivo and in vitro data.

    abstract::The data of nine monolayer cultures, 48 multicellular spheroids, and 19 s.c. xenografts of LoVo cells were fitted, on an individual basis, by exponential and Gompertzian equations, respectively. The mean growth parameters alpha 0 (initial growth rate) and beta (retardation factor) of the three experimental systems pre...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Demicheli R,Foroni R,Ingrosso A,Pratesi G,Soranzo C,Tortoreto M

    更新日期:1989-12-01 00:00:00

  • NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations.

    abstract::Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is a common event in human cancer, either through inactivation of the tumor suppressor phosphatase and tensin homologue deleted from chromosome 10 or activating mutations of p110-alpha. These hotspot mutations result in oncogenic activity of the enzyme and cont...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-1385

    authors: Serra V,Markman B,Scaltriti M,Eichhorn PJ,Valero V,Guzman M,Botero ML,Llonch E,Atzori F,Di Cosimo S,Maira M,Garcia-Echeverria C,Parra JL,Arribas J,Baselga J

    更新日期:2008-10-01 00:00:00

  • Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4-STAT3 signaling.

    abstract::Infiltrating macrophages are a key component of inflammation during tumorigenesis, but the direct evidence of such linkage remains unclear. We report here that persistent coculturing of immortalized prostate epithelial cells with macrophages, without adding any carcinogens, induces prostate tumorigenesis and that indu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-3228

    authors: Fang LY,Izumi K,Lai KP,Liang L,Li L,Miyamoto H,Lin WJ,Chang C

    更新日期:2013-09-15 00:00:00

  • Osteoclasts direct bystander killing of bone cancer.

    abstract::Primary and metastatic bone cancers are difficult to eradicate and novel approaches are needed to improve treatment and extend life. As bone cancer grows, osteoclasts, the principal bone-resorbing cells of the body, are recruited to and activated at sites of cancer. In this investigation, we determined if osteoclast l...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-1295

    authors: Ramnaraine ML,Mathews WE,Donohue JM,Lynch CM,Goblirsch MJ,Clohisy DR

    更新日期:2006-11-15 00:00:00

  • Karyotypic changes associated with loss of prolactin dependency of rat Nb2 node lymphoma cell cultures.

    abstract::The parent line of cultured "Nb2 node" lymphoma cells is dependent on the hormone prolactin (PRL) for growth and is widely used for the in vitro bioassay of lactogenic hormones. As reported previously, PRL-independent sublines have been developed in vitro from the parental line by lactogen deprivation. The present stu...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Horsman DE,Masui S,Gout PW

    更新日期:1991-01-01 00:00:00

  • Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium.

    abstract::Type beta transforming growth factor-growth inhibitor (TGF beta/GI) causes normal human prokeratinocytes to arrest growth predominantly in the G1 phase of the cell cycle within 48 h after log phase cultures are exposed to the factor in serum-free medium. The growth arrest induced by TGF beta/GI is reversible because t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Shipley GD,Pittelkow MR,Wille JJ Jr,Scott RE,Moses HL

    更新日期:1986-04-01 00:00:00

  • Coordinated induction of autocrine tumor necrosis factor and interleukin 1 in normal human monocytes and the implications for monocyte-mediated cytotoxicity.

    abstract::Cytokine production and cytotoxicity for tumor cells are two important aspects of monocyte function and the inflammatory response against tumors and infectious agents. In the present studies we provide direct evidence at the mRNA and protein levels for the existence of autocrine tumor necrosis factor (TNF) and its imp...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Smith DM,Lackides GA,Epstein LB

    更新日期:1990-06-01 00:00:00

  • Differential expression of c-myc gene and c-fos gene in premalignant and malignant tissues from patients with familial polyposis coli.

    abstract::The expression of 8 oncogenes and the structures of 19 oncogenes were analyzed in 15 adenocarcinomas (12 primary and 3 metastatic), 18 adenomatous polyps, and 18 normal colonic mucosae derived from 19 patients with familial polyposis coli. The expression of c-myc gene was most elevated in carcinoma, and moderately ele...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Sugio K,Kurata S,Sasaki M,Soejima J,Sasazuki T

    更新日期:1988-09-01 00:00:00

  • Differential regulation of cyclin-dependent kinase inhibitors in monolayer and spheroid cultures of tumorigenic and nontumorigenic fibroblasts.

    abstract::The Ras proto-oncogene has been implicated in the in vivo development of tumors and in the in vitro transformation of cultured cell lines. In both of these conditions, Ras-mediated disruption of cell cycle-regulatory mechanisms leads to unregulated cellular proliferation, although the exact mechanisms by which Ras acc...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: LaRue KE,Bradbury EM,Freyer JP

    更新日期:1998-03-15 00:00:00