Abstract:
:Hormonal therapies targeting androgen receptor (AR) are effective in prostate cancer (PCa), but often the cancers progress to fatal castrate-resistant disease. Improved understanding of the cellular events during androgen deprivation would help to identify survival and stress pathways whose inhibition could synergize with androgen deprivation. Toward this aim, we performed an RNAi screen on 2,068 genes, including kinases, phosphatases, epigenetic enzymes and other druggable gene targets. High-content cell spot microarray (CSMA) screen was performed in VCaP cells in the presence and absence of androgens with detection of Ki67 and cleaved ADP-ribose polymerase (cPARP) as assays for cell proliferation and apoptosis. Thirty-nine candidate genes were identified, whose silencing inhibited proliferation or induced apoptosis of VCaP cells exclusively under androgen-deprived conditions. One of the candidates, HSPB (heat shock 27 kDa)-associated protein 1 (HSPBAP1), was confirmed to be highly expressed in tumor samples and its mRNA expression levels increased with the Gleason grade. We found that strong HSPBAP1 immunohistochemical staining (IHC) was associated with shorter disease-specific survival of PCa patients compared with negative to moderate staining. Furthermore, we demonstrate that HSPBAP1 interacts with AR in the nucleus of PCa cells specifically during androgen-deprived conditions, occupies chromatin at PSA/klk3 and TMPRSS2/tmprss2 enhancers and regulates their expression. In conclusion, we suggest that HSPBAP1 aids in sustaining cell viability by maintaining AR signaling during androgen-deprived conditions.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Saeed K,Östling P,Björkman M,Mirtti T,Alanen K,Vesterinen T,Sankila A,Lundin J,Lundin M,Rannikko A,Nordling S,Mpindi JP,Kohonen P,Iljin K,Kallioniemi O,Rantala JKdoi
10.1002/ijc.29303subject
Has Abstractpub_date
2015-06-01 00:00:00pages
2535-45issue
11eissn
0020-7136issn
1097-0215journal_volume
136pub_type
杂志文章abstract::Our study was designed to examine the effects of IL-2 gene therapy in a surgical minimal residual tumour disease (SMRTD). Mice were inoculated s.c. with methylcholanthrene (MC)-induced MC12 sarcoma cells. When the tumours reached 8 to 12 mm in diameter, they were excised, either completely ("microscopic SMRTD") or inc...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19980330)76:1<115::aid-ijc
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abstract::Effects of therapeutic and supratherapeutic concentrations of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, on the corrected QT interval (QTc) in 60 healthy adults were assessed, according to ICH-E14 guidelines, in this 2-part, randomized, single-dose, double-blind, crossover, placebo- and open-label moxifloxac...
journal_title:International journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/ijc.27348
更新日期:2012-08-01 00:00:00
abstract::It is currently under debate whether the low serum cholesterol levels that are frequently observed in cancer patients represent a risk factor for/or, rather, are a consequence of the tumour. We postulate that malignant tumours are directly involved in an increased catabolism of cholesterol-rich low-density lipoprotein...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910610405
更新日期:1995-05-16 00:00:00
abstract::The subsets of small lymphocytes (surface Igm-positive or B, Thy-I-positive or T and "double-negative" or null) appearing within spontaneous mammary tumors of C3H retired breeder female mice and in various lymphoid organs of the host at different stages of tumor development were characterized directly using a radioaut...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910250122
更新日期:1980-01-15 00:00:00
abstract::Macrophages were isolated from 22 human ascitic ovarian epithelial tumors and their growth-inhibitory capacity was tested using as targets the following in vitro tumor cell lines: murine TLX9 lymphoma and FS6 sarcoma; human myeloid K562 leukemia and human E cell line derived from an ovarian carcinoma. Macrophage prepa...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910230204
更新日期:1979-02-01 00:00:00
abstract::A panel of monoclonal antibodies (MAbs) has been obtained, directed against determinants of normal human colorectal epithelium. BALB/c mice were immunized and boosted with mucosal scrapings and cell membrane preparations from normal large intestine. In one case boosting was also performed with HT29 colon carcinoma cel...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910390309
更新日期:1987-03-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991029)83:3<374::aid-ijc
更新日期:1999-10-29 00:00:00
abstract::Rabbits were immunized with extracts of primary or grafted intestinal adeno-carcinomas induced by carcinogenic drugs in inbred rats. After absorption with normal tissue extracts, the antisera were able to recognize three tumor-associated antigens. Two of them were glycoproteins, present in cancer cells but also, in tr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910150117
更新日期:1975-01-15 00:00:00
abstract::To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy number of the c-myc gene were determined. Expression of mRNA was measured by quantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically normal mucosae. Mean e...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990420)84:2<169::aid-ijc
更新日期:1999-04-20 00:00:00
abstract::A randomized screening trial was started in Europe to show the effect of early detection and treatment of prostate cancer on mortality (European Study on Screening of Prostate Cancer). In one centre (Rotterdam), the screening protocol initially consisted of 3 screening tests for all men: prostate-specific antigen (PSA...
journal_title:International journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/(sici)1097-0215(19990820)84:4<437::aid-ijc
更新日期:1999-08-20 00:00:00
abstract::The UBE1L gene isolated from the chromosome 3p21 region has an extremely reduced level of mRNA in lung cancer. Sequence analysis showed a 45% homology to the human ubiquitin-activating enzyme E1 at the amino acid level. To further characterize the protein product, we generated UBE1L protein-specific antibodies. Immuno...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(20000315)85:6<871::aid-ijc
更新日期:2000-03-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910600420
更新日期:1995-02-08 00:00:00
abstract::We show that siRNA-mediated suppression of protein tyrosine phosphatase alpha (PTP alpha) reduces Src activity 2 to 4-fold in breast, colon and other human cancer cell lines. Src and PTP alpha RNAi induced apoptosis in estrogen receptor (ER)-negative breast cancer and colon cancer cells, but not in immortalized noncan...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23321
更新日期:2008-05-01 00:00:00
abstract::The anti-tumor effects of actinomycin D (Act D) and recombinant human tumor necrosis factor (TNF)-alpha have been studied on 4 established murine tumor cell lines: MmB16 melanoma, Lewis lung (LL/2) carcinoma, L1 sarcoma and L1210 leukemia. During short-term incubation (24 hr) Act D produced dose-dependent cytostatic/c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960503)66:3<374::AID-IJC
更新日期:1996-05-03 00:00:00
abstract::A syngeneic tumor system in DBA/2 mice consisting of a methyl-cholanthrene-induced, weakly metastatic lymphoma, L5178YE (= Eb), its spontaneous strongly metastatic variant, L5178YES (= ESb), and an unrelated, methylcholanthrene-induced, metastasizing tumor, MDAY-D2, were used to study the relationship between metastat...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360514
更新日期:1985-11-15 00:00:00
abstract::Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970822)74:4<407::aid-ijc
更新日期:1997-08-22 00:00:00
abstract::Administration of highly purified interferon to DBA/2 mice inhibited the growth of interferon-sensitive or interferon-resistant Friend erythroleukemia cells implanted subcutaneously. Injection of interferon at the site of tumor inoculation was more effective than injection of interferon intraperitoneally. Histologic e...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910310518
更新日期:1983-05-15 00:00:00
abstract::Abnormal survivin expression has been reported to be involved in many types of cancer. A single-nucleotide polymorphism (SNP), C-31G, located in the promoter region of survivin reportedly may alter the mRNA level, while the significance of the nonsynonymous SNP A9194G in exon 4 has not yet been clarified. Here, the as...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2011-10-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2009-08-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910400108
更新日期:1987-07-15 00:00:00
abstract::The ability of verapamil to overcome resistance to adriamycin in a multidrug-resistant derivative of the V79 cell line (LZ), grown as multicellular spheroids or as monolayers, was examined. Verapamil was much less effective in overcoming resistance to adriamycin in spheroids than in monolayers. Verapamil increased the...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910590222
更新日期:1994-10-15 00:00:00
abstract::Evidence indicates that acquired resistance of cancers to chemotherapeutic agents can occur via epigenetic mechanisms. Down-regulation of expression of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in the biosynthesis of arginine, has been associated with the development of platinum resistance in ovari...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24546
更新日期:2009-09-15 00:00:00
abstract::Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 participants in the Nurses' Health Study (NHS) and 105,386 of the Nurses' Health Study II (N...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29427
更新日期:2015-08-01 00:00:00
abstract::Inactivation of the tumor suppressor gene, von Hippel-Lindau (VHL), is known to play an important role in the development of sporadic clear cell renal cell carcinomas (ccRCCs). Even if available targeted therapies for metastatic RCCs (mRCCs) have helped to improve progression-free survival rates, they have no durable ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30774
更新日期:2017-08-15 00:00:00
abstract::Cutaneous T-Cell lymphoma (CTCL) is a non-Hodgkin's lymphoma of unknown pathogenesis. Mycosis fungoides (MF) is a clinically determined subset of CTCL with intensive infiltration of lymphoma cells into the epidermis. To determine whether Epstein-Barr virus (EBV) is associated with these lymphoma cells, we performed mR...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(200102)9999:9999<::aid-ijc1172>3
更新日期:2001-04-15 00:00:00
abstract::Transforming growth factor-beta (TGF-beta) receptors constitute a family of transmembrane proteins that bind TGF-beta ligands. In this study we assessed the growth responsiveness to TGF-beta 1 in pancreatic cancer cell lines and characterized the levels of expression of TGF-beta receptors in these cell lines and in hu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960717)67:2<283::AID-IJC
更新日期:1996-07-17 00:00:00
abstract::TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10540
更新日期:2002-08-20 00:00:00
abstract::The variants within the human melanocortin 1 receptor (MC1R) gene are associated with an increased risk of different skin cancers. In this study, we genotyped by direct sequencing, 529 cases of basal cell carcinoma of the skin (BCC) and 533 healthy controls for polymorphisms in the entire MC1R gene. In addition to 10 ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23257
更新日期:2008-04-15 00:00:00
abstract::A panel of 7 mouse monoclonal antibodies and the lectin from Ulex europeus, detecting blood-group-related antigens of the ABH and Lewis systems, have been used to define the distribution of these antigenic structures within the human gastrointestinal tract, and to characterize their expression and modulation in colore...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910370505
更新日期:1986-05-15 00:00:00
abstract::Treatment of lung cancer is often performed with cone-down oblique beams to spare spinal cord and normal structures. However, there is no optimum technique to determine oblique beam angles when a CT simulation is not available. Impact of oblique beam angle was investigated in this study. Fifteen patients with centrall...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/1097-0215(20001220)90:6<359::aid-ijc8>3.0.
更新日期:2000-12-20 00:00:00