- Research article
- Open Access
- Open Peer Review
This article has Open Peer Review reports available.
FGFR1 and WT1 are markers of human prostate cancer progression
© Devilard et al; licensee BioMed Central Ltd. 2006
Received: 09 October 2006
Accepted: 30 November 2006
Published: 30 November 2006
Androgen-independent prostate adenocarcinomas are responsible for about 6% of overall cancer deaths in men.
We used DNA microarrays to identify genes related to the transition between androgen-dependent and androgen-independent stages in the LuCaP 23.1 xenograft model of prostate adenocarcinoma. The expression of the proteins encoded by these genes was then assessed by immunohistochemistry on tissue microarrays (TMA) including human prostate carcinoma samples issued from 85 patients who had undergone radical prostatectomy.
FGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples. MART1 protein expression was correlated with pT2 tumor stages.
Our results suggest that each of these four genes may play a role, or at least reflect a stage of prostate carcinoma growth/development/progression.
Prostate adenocarcinoma is the most common cancer in men in western countries, and is responsible for about 6% of overall cancer deaths . Localized prostate adenocarcinoma is usually treated by either surgery or radiotherapy. In the early stages, tumor growth is dependent on androgen stimulus and androgen ablation may be used as a complementary therapy. The tumor then progresses to an androgen-independent stage against which hormone therapy has no effect. Currently, there is no effective therapy against androgen-independent prostate cancer.
The molecular biology of prostate cancer is not well understood. Several previous reports have proposed candidate molecules linked to hereditary prostate cancer [3, 4]. GSTP1, PTEN, TP53, and androgen receptor (AR) are mutated or deregulated in sporadic prostate cancer  and may become targets for innovative therapies. Recently, DNA microarrays experiments have identified other potential prognostic markers and/or targets, such as Hepsin/TMPRSS1, PSMA, and MMR genes [6, 7] and gene fusions . Overall, little is known about the progression from androgen-dependent to androgen-independent stages .
The LuCaP 23.1 human prostate carcinoma xenograft model  mimics the different stages of tumor growth and may be an adequate system to identify the molecular events associated with cancer progression . Like for human samples, DNA microarray analyses of xenograft model systems have led to the discovery of several genes associated with cancer progression. However, although xenograft model systems are invaluable for gene discovery studies, as well as for experimental therapeutics, there is concern that growth of human cancer cells in an immunocompromised mouse host may not always be representative of progression of cancer in patients . Combined gene and protein expression profilings – e.g. DNA microarrays and tissue microarrays (TMA)  – may allow easier or quicker validation of results provided by xenograft studies.
In the present work, we used DNA microarrays to identify candidate genes correlated with progression to androgen-resistant stage in the LuCaP 23.1 xenograft model. The expression of candidate genes with available and well-performing antibody was then assessed by immunohistochemistry (IHC) on TMA including human prostate carcinoma samples from 85 patients who had undergone radical prostatectomy.
Patients and tumor characteristics.
All patients (n = 85)
Median age (years)
Median follow-up (months)
Metastatic relapse (n)
LuCaP 23.1 xenograft model
Fresh frozen tumor samples were obtained from four different mice bearing the LuCaP 23.1 xenograft . Each mouse was sampled three times, reflecting three distinct stages of tumor progression: primary tumor (day 1 post-transplantation), hormone sensitive (HS) tumor (day 7 post-transplantation), and hormone refractory (HR) tumor (day 114 post- transplantation).
Total RNA was extracted from tissue samples by lysis in guanidium isothiocyanate and centrifugation over a cesium chloride cushion following standard protocols . RNA quality was assessed by denaturing formaldehyde agarose gel electrophoresis and reverse-transcribed PCR (RT-PCR) amplification of the β2-microglobulin transcript.
DNA microarrays preparation and analysis
We used DNA microarrays to compare the mRNA expression profiles of ~1.000 selected genes between primary, HS, and HR tumors in the LuCaP 23.1 xenograft model of prostate carcinoma. RNA extracts were pooled according to the three distinct stages of tumor progression in the LuCaP 23.1 model (4 samples/tumor stage). DNA microarray hybridizations were done as previously described [14, 15] on home-made nylon DNA microarrays (TAGC, Marseille-Luminy, France), which contained spotted PCR products from 945 human cDNA clones. Most genes were selected for a proven or putative implication in cancer and/or in immune reactions. Microarrays were hybridized with 33P-labeled probes made from 5 μg of total RNA. Probe preparations, hybridizations, and washes were done as previously described . Briefly, 5 μg of total RNA were retrotranscribed in the presence of [-33P] dCTP (Amersham Biosciences). Hybridizations were done during 48 hours at 68°C in a final volume of 10 mL of buffer. After washes, arrays were exposed for 24 hours to phosphorimaging plates. Detection scanning was done with a FUJI BAS 5000 machine at 25-μm resolution (Raytest, Paris, France) and quantification of hybridization signals with the ArrayGauge software (Fuji Ltd, Tokyo, Japan). All hybridization images were inspected for artifacts, and aberrant spots or microarray regions were excluded from analyses. Data were analyzed as previously reported . Hierarchical clustering was applied to the tissue samples and the genes using the Cluster program developed by Eisen .
All data are compliant with Minimum Information about Microarray Experiment (MIAME) guidelines and have been submitted to Gene Expression Omnibus (GEO) database [GEO: GSE6284].
Tissue microarray (TMA) construction
The TMA included 96 formalin-fixed, paraffin-embedded human prostate tissue samples. TMA was prepared as described  with slight modifications. For each tumor, one representative tumor area was carefully selected from a hematoxylin- and eosin-stained section of a donor block. Core cylinders with a diameter of 1,2 mm each were punched from each of these areas and deposited into a recipient paraffin block using a specific arraying device (Beecher Instruments, Silver Spring, MD). Five-μm sections of the resulting microarray block were made and used for IHC analysis after transfer to glass slides.
Antibodies and antigen retrieval procedures used for IHC
Primers used for mRNA amplification by RT-PCR.
PCR conditions for RT-PCR amplification
N° of cycles
Overexpression of FGFR1, MART1, TACC1, and WT1 mRNAs in tumor progression in the LuCaP 23.1 carcinoma model
27 and 9 genes differentially expressed between primary and HR, and between primary and HS LuCaP 23.1 xenografts.
HR vs LUCAP 23.1
Fibroblast growth factor receptor 1
Cyclin-dependent kinase 4
Autocrine motility factor receptor
Vegf receptor 1/FLT1
Integrin alpha 3/CD49C
Polymorphic epithelial mucin
NFKb, p65 subunit
Serum response factor
MAX transcription regulator
Neogenin homolog 1
Integrin beta 5
Retinoic X receptor alpha
Insulin-like growth factor binding protein
CREB binding protein
Membrane-type matrix metalloproteinase 2
MAD homolog 9
Apoptosis regulator bak
92 kDa gelatinase, matrix metalloproteinase-9
GATA-binding protein 1
ATP-binding cassette, sub-family C, member 5
PP2A BR gamma
Frizzled 5, WNT pathway
HS vs LuCaP 23.1
Nuclear receptor liver X receptor
Stathmin, phosphoprotein p19
signal transducer and activator of transcription 1
Cas-Br-M ectropic retroviral transforming sequence b
WNT factor 2
FGFR1, TACC1 and WT1 proteins display high levels of expression in advanced stages of human prostate carcinoma
We then assessed the expression of four candidate proteins – FGFR1, MART1, TACC1 and WT1 – in human prostate carcinoma samples by IHC. This choice was supported by the availability of a corresponding antibody performing well on paraffin-embedded sections. To this purpose, we constructed a TMA that included 85 prostate carcinoma samples from 85 patients and 11 benign prostate tissue samples issued from 11 of these 85 patients.
Expression of FGFR1, MART1, TACC1 and WT1 proteins in human prostate cancer.
No. of patients (%)
MART1, TACC1, and WT1 mRNA levels in human prostate samples correlate with IHC findings
MART1 mRNA was weakly expressed in only 1/6 pT2 carcinoma, without any expression in pT3 carcinoma or HR (N1 and/or M1) samples (Figure 3). TACC1 mRNA expression was stronger in pT2 and pT3 carcinomas than in benign prostate tissue samples (Figure 3). Furthermore, TACC1 mRNA expression was strong in HR stage carcinoma samples (Figure 3). A WT1 mRNA variant (706 bp) was expressed in 2 of 6 pT2 carcinoma samples, while the major WT1 mRNA was strongly expressed in pT3 and HR (N1 and/or M1) carcinoma samples.
Using three methods of analysis (DNA microarrays, TMA, and RT-PCR), we have shown that FGFR1, TACC1 and WT1 have much higher levels of expression in human prostate carcinoma than in benign prostate tissue samples, at both mRNA and protein levels. We have also found that FGFR1 and WT1 mRNA are preferentially expressed in pT3 and/or N1/M1 carcinoma samples, and that MART1 expression is correlated with HS stage LuCaP 23.1 carcinoma and pT2 prostate carcinoma.
High-throughput screening techniques provide opportunities to identify new diagnostic or prognostic markers and innovative therapeutic targets in the whole field of oncology. TMA is a powerful tool to validate DNA microarrays data and extend the scope of gene expression profiling to the post-transcriptional level. Several previous studies [17, 20, 22, 23] have emphasized how TMAs are useful to validate the use of candidate prostate carcinoma markers in routine (IHC) conditions .
Potential new markers for prostate cancer progression
We found that expression of FGFR1, WT1, and, to a lesser extent, TACC1 protein is upregulated in advanced stages (pT3 and/or N1/M1) of prostate cancer, whereas MART1 is mainly expressed in localized (pT2) stage prostate cancer. In the same way, we observed that the corresponding mRNAs – FGFR1, TACC1, and WT1 on the one hand, and MART1 on the other hand – are overexpressed in HR and HS stage LuCaP 23.1 prostate carcinoma, respectively.
FGFR1 codes for a tyrosine kinase receptor for members of the FGF family of growth factors. It is a potential oncogene, amplified in breast cancers and rearranged in hematopoietic diseases. The case of FGFR1 in prostate cancer is rather clear and our results are in perfect agreement with previous data. Expression of FGFR1 is associated with increased proliferation and aggressive behavior of prostate cancer [24, 25].
The MelanA/MART1 gene encodes a tyrosinase that is a marker of melanocytic differentiation . It can be recognized by cytotoxic T cells  and has been considered as a target for immunotherapy . A previous study has shown that the protein is expressed in lymph nodes from breast cancer patients . Our results showed mRNA overexpression in HS stage LuCaP 23.1 model and IHC expression of MART1 in about 20% of prostate carcinomas, mainly pT2 stages. MART1 expression was strictly restricted to carcinoma cells, without any staining in benign prostate tissue. Therefore, we suggest that MART1 may be a marker of some intermediate, hormone sensitive stage of prostate carcinoma, and that its transient expression might be shut down during cancer progression towards hormone resistant and/or advanced clinical stages (T3 and/or N+ and/or M+).
TACC1 belongs to the TACC/taxins (Transforming Acidic Coiled-Coil) protein family. Taxins are centrosome and spindle-associated proteins involved in cell division . Mammalian Taxins are probably involved in oncogenesis in different ways [29, 30]. TACC1 maps to 8p11, a region that is amplified and rearranged in many malignancies [29–31]. We observed upregulation of TACC1 expression in prostate carcinoma. This is in agreement with previous reports focusing on other tumors . Since we found TACC1 underexpressed in the majority of breast carcinoma , TACC1 role remains to be determined. As previously suggested, TACC1 might be involved in multiple complexes that may be deregulated in malignant conditions .
The WT1 (Wilms tumor 1) gene encodes a zinc finger transcription factor that modulates the expression of several genes encoding growth factors and receptors (epidermal growth factor receptor , insulin-like growth factor II , IGF1 receptor  and AR . In Wilms tumor, different point mutations have been described in the WT1 locus, suggesting that WT1 altered protein may be directly involved in tumor formation. High WT1 expression levels have been reported in several malignancies [38–41], and have been linked to a poor prognosis . WT1 expression and multidrug resistance are associated in some hematological malignancies, suggesting that WT1 may be a marker for chemoresistance . We found high expression levels of WT1 in pT3 stage carcinoma samples, and expression of wild-type WT1 mRNA in both advanced stages (≥ pT3) and HR stage LuCaP 23.1 carcinomas. These results suggest that WT1 expression in prostate carcinoma may be associated with progression towards hormone resistance and that WT1 may be considered as a potential hormone resistance and prognostic marker in human prostate carcinoma. These hypotheses are supported by the strong repression of AR promoter by WT1 .
We thank F. Birg and D. Maraninchi for encouragements. This work was supported by Institut Paoli-Calmettes and INSERM.
- Parkin DM, Bray FI, Devesa S: Cancer burden in the year 2000. The global picture. Eur J Cancer. 2001, 37 (supplt 8): SA-S66.Google Scholar
- Feldman BJ, Feldman D: The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001, 1 (1): 34-45. 10.1038/35094009.View ArticlePubMedGoogle Scholar
- Isaacs W, Kainu T: Oncogenes and tumor suppressor genes in prostate cancer. Epidemiol Rev. 2001, 23 (1): 36-41.View ArticlePubMedGoogle Scholar
- Ostrander EA, Markianos K, Stanford JL: Finding prostate cancer susceptibility genes. Annu Rev Genomics Hum Genet. 2004, 5: 151-75. 10.1146/annurev.genom.5.061903.180044.View ArticlePubMedGoogle Scholar
- Porkka KP, Visakorpi T: Molecular mechanisms of prostate cancer. Eur Urol. 2004, 45 (6): 683-91. 10.1016/j.eururo.2004.01.012.View ArticlePubMedGoogle Scholar
- Landers KA, Burger MJ, Tebay MA, Purdie DM, Scells B, Samaratunga H, Lavin MF, Gardiner RA: Use of multiple biomarkers for a molecular diagnosis of prostate cancer. Int J Cancer. 2005, 950-6. 10.1002/ijc.20760.Google Scholar
- Fromont G, Chene L, Vidaud M, Vallancien G, Mangin P, Fournier G, Validire P, Latil A, Cussenot O: Abstract Differential expression of 37 selected genes in hormone-refractory prostate cancer using quantitative taqman real-time RT-PCR. Int J Cancer. 2005, 114 (2): 174-81. 10.1002/ijc.20704.View ArticlePubMedGoogle Scholar
- Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM: Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005, 310 (5748): 644-8. 10.1126/science.1117679.View ArticlePubMedGoogle Scholar
- Ellis WJ, Vessella RL, Buhler KR, Bladou F, True LD, Bigler SA, Curtis D, Lange PH: Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23. Clin Cancer Res. 1996, 2 (6): 1039-48.PubMedGoogle Scholar
- Mousses S, Wagner U, Chen Y, Kim JW, Bubendorf L, Bittner M, Pretlow T, Elkahloun AG, Trepel JB, Kallioniemi OP: Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling. Oncogene. 2001, 20 (46): 6718-23. 10.1038/sj.onc.1204889.View ArticlePubMedGoogle Scholar
- Van Weerden WM, Romijn JC: Use of nude mouse xenograft models in prostate cancer research. Prostate. 2000, 43 (4): 263-271. 10.1002/1097-0045(20000601)43:4<263::AID-PROS5>3.0.CO;2-I.View ArticlePubMedGoogle Scholar
- Kononen J, Budendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Tohorst J, Mihatsch MJ, Suater J, Kallioniemi OP: Tissue Microarrays for high-throughput molecular profiling of tumor specimens. Nat Med. 1998, 4 (7): 844-847. 10.1038/nm0798-844.View ArticlePubMedGoogle Scholar
- Theillet C, Adelaide J, Louason G, Bonnet-Dorion F, Jacquemier J, Adane J, Longy M, Katsaros D, Sismondi P, Gaudray P, Birnbaum D: FGFRI and PLAT genes and DNA amplification at 8p12 in breast and ovarian cancers. Genes Chromosomes Cancer. 1993, 7 (4): 219-226.View ArticlePubMedGoogle Scholar
- Bertucci F, Nasser V, Granjeaud S, Eisinger F, Adelaide J, Tagett R, Loriod B, Giaconia A, Benziane A, Devilard E, Jacquemier J, Viens P, Nguyen C, Birnbaum D, Houlgatte R: Gene expression profiles of poor-prognosis primary breast cancer correlate with survival. Hum Mol Genet. 2002, 11 (8): 863-72. 10.1093/hmg/11.8.863.View ArticlePubMedGoogle Scholar
- Devilard E, Bertucci F, Trempat P, Bouabdallah R, Loriod B, Giaconia A, Brousset P, Granjeaud S, Nguyen C, Birnbaum D, Birg F, Houlgatte R, Xerri L: Gene expression profiling defines molecular subtypes of classical Hodgkin's disease. Oncogene. 2002, 21 (19): 3095-3102. 10.1038/sj.onc.1205418.View ArticlePubMedGoogle Scholar
- Eisen MB, Spellman PT, Brown PO, Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA. 1998, 95 (25): 14863-14868. 10.1073/pnas.95.25.14863.View ArticlePubMedPubMed CentralGoogle Scholar
- Richter J, Wagner U, Kononen J, Fijan A, Bruderer J, Schmid U, Ackerman D, Maurer R, Alund G, Knönagel H, Rist M, Wilber K, Anabitarte M, Hering F, Hardmeier T, Schönenberger A, Flury R, Jäger P, Fehr JL, Schrami P, Moch H, Mihatsch MJ, Gasser T, Kallioniemi OP, Sauter G: High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer. Am J Pathol. 2000, 157 (3): 787-794.View ArticlePubMedPubMed CentralGoogle Scholar
- Bertucci F, Van Hulst S, Bernard K, Loriod B, Granjeaud S, Tagett R, Starkey M, Nguyen C, Jordan B, Birnbaum D: Expression scanning of an array of growth control genes in human tumor cell lines. Oncogene. 1999, 18 (26): 3905-3912. 10.1038/sj.onc.1202731.View ArticlePubMedGoogle Scholar
- Edwards J, Krishna NS, Witton CJ, Bartlett JM: Gene amplifications associated with the development of hormone-resistant prostate cancer. Clin Cancer Res. 2003, 9 (14): 5271-81.PubMedGoogle Scholar
- Jacquemier J, Ginestier C, Rougemont J, Bardou VJ, Charafe-Jauffret E, Geneix J, Adelaide J, Koki A, Houvenaeghael G, Hassoun J, Maraninchi D, Viens P, Birbaum D, Bertucci F: Protein expression profiling identifies subclasses of breast cancer and predicts prognosis. Cancer Res. 2005, 65 (3): 767-79.PubMedGoogle Scholar
- Varambally S, Yu J, Laxman B, Rhodes DR, Mehra R, Tomlins SA, Shah RB, Chandran U, Monzon FA, Becich MJ, Wei JT, Pienta KJ, Ghosh D, Rubin MA, Chinnaiyan AM: Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell. 2005, 8 (5): 393-406. 10.1016/j.ccr.2005.10.001.View ArticlePubMedGoogle Scholar
- Amler LC, Agus DB, LeDuc C, Sapinoso ML, Fox WD, Kern S, Lee D, Wang V, Leysens M, Higgins B, Martin J, Gerald W, Dracopoli N, Cordon-Cardo C, Scher HI, Hampton GM: Dysregulated expression of androgen-responsive and nonresponsive genes in the androgen-independent prostate cancer xenograft model CWR22-R1. Cancer Res. 2000, 60 (21): 6134-4.PubMedGoogle Scholar
- Mousses S, Bubendorf L, Wagner U, Hostetter G, Kononen J, Cornelison R, Goldberger N, Elkahloun AG, Willi N, Koivisto P, Ferhle W, Raffeld M, Sauter G, Kallioniemi OP: Clinical validation of candidate genes associated with prostate cancer progression in the CWR22 model system using tissue microarrays. Cancer Res. 2002, 62 (5): 1256-60.PubMedGoogle Scholar
- Feng S, Wang F, Matsubara A, Kan M, McKeehan WL: Fibroblast growth factor receptor 2 limits and receptor 1 acceleratestumorigenicity of prostate epithelial cells. Cancer Res. 57 (23): 5369-78. 1997 Dec 1Google Scholar
- Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA: Expression of bFGF/FGFR-1 and vascular proliferation related to clinicopathologicfeatures and tumor progress in localized prostate cancer. Virchows Arch. 2006, 448 (1): 68-74. 10.1007/s00428-005-0075-3. Epub 2005 Oct 12View ArticlePubMedGoogle Scholar
- Busam KJ, Chen YT, Old LJ, Stockert E, Iversen K, Coplan KA, Rosai J, Barnhill RL, Jungbluth AA: Expression of melan-A (MART1) in benign melanocytic nevi and primary cutaneous malignant melanoma. Am J Surg Pathol. 1998, 22 (8): 976-82. 10.1097/00000478-199808000-00007.View ArticlePubMedGoogle Scholar
- Yan S, Brennick JB: False-positive rate of the immunoperoxidase stains for MART1/MelanA in lymph nodes. Am J Surg Pathol. 2004, 28 (5): 596-600.View ArticlePubMedGoogle Scholar
- Rivoltini L, Squarcina P, Loftus DJ, Castelli C, Tarsini P, Mazzocchi A, Rini F, Viggiano V, Belli F, Parmiani G: A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy. Cancer Res. 1999, 59 (2): 301-6.PubMedGoogle Scholar
- Gergely F, Kidd D, Jeffers K, Wakefield JG, Raff JW: D-TACC: a novel centrosomal protein required for normal spindle function in the early Drosophila embryo. EMBO J. 2000, 19 (2): 241-52. 10.1093/emboj/19.2.241.View ArticlePubMedPubMed CentralGoogle Scholar
- Still IH, Hamilton M, Vince P, Wolfman A, Cowell JK: Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. Oncogene. 1999, 18 (27): 4032-8. 10.1038/sj.onc.1202801.View ArticlePubMedGoogle Scholar
- Still IH, Vince P, Cowell JK: The third member of the transforming acidic coiled coil-containing gene family, TACC3, maps in 4p16, close to translocation breakpoints in multiple myeloma, and is upregulated in various cancer cell lines. Genomics. 1999, 58 (2): 165-70. 10.1006/geno.1999.5829.View ArticlePubMedGoogle Scholar
- Chen HM, Schmeichel KL, Mian IS, Lelievre S, Petersen OW, Bissell MJ: AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression. Mol Biol Cell. 2000, 11 (4): 1357-67.View ArticlePubMedPubMed CentralGoogle Scholar
- Ugolini F, Adelaide J, Charafe-Jauffret E, Nguyen C, Jacquemier J, Jordan B, Birnbaum D, Pebusque MJ: Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes. Oncogene. 1999, 18 (10): 1903-10. 10.1038/sj.onc.1202739.View ArticlePubMedGoogle Scholar
- Conte N, Charafe-Jauffret E, Delaval B, Adelaide J, Ginestier C, Geneix J, Isnardon D, Jacquemier J, Birnbaum D: Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. Oncogene. 2002, 21 (36): 5619-30. 10.1038/sj.onc.1205658.View ArticlePubMedGoogle Scholar
- Wang ZY, Qiu QQ, Enger KT, Deuel TF: A second transcriptionally active DNA-binding site for the Wilms tumor gene product, WT1. Proc Natl Acad Sci. 1993, 90 (19): 8896-900. 10.1073/pnas.90.19.8896.View ArticlePubMedPubMed CentralGoogle Scholar
- Werner H, Roberts CT, Rauscher FJ, LeRoith D: Regulation of insulin-like growth factor I receptor gene expression by the Wilms' tumor suppressor WT1. J Mol Neurosci. 1996, 7 (2): 111-23. 10.1016/S0165-0270(96)00108-2.View ArticlePubMedGoogle Scholar
- Shimamura R, Fraizer GC, Trapman J, Lau YfC, Saunders GF: The Wilms' tumor gene WT1 can regulate genes involved in sex determination and differentiation: SRY, Mullerian-inhibiting substance, and the androgen receptor. Clin Cancer Res. 1997, 3 (12): 2571-80.PubMedGoogle Scholar
- Tamaki H, Ogawa H, Ohyashiki K, Ohyashiki JH, Iwama H, Inoue K, Soma T, Oka Y, Tatekawa T, Oji Y, Tsuboi A, Kim EH, Kawakami M, Fuchigami K, Tomonaga M, Toyama K, Aozasa K, Kishimoto T, Sugiyama H: The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. Leukemia. 1999, 13 (3): 393-9. 10.1038/sj/leu/2401341.View ArticlePubMedGoogle Scholar
- Trka J, Kalinova M, Hrusak O, Zuna J, Krejci O, Madzo J, Sedlacek P, Vavra V, Michalova K, Jarosova M, Stary J: Real-time quantitative PCR detection of WT1 gene expression in children with AML: prognostic significance, correlation with disease status and residual disease detection by flow cytometry. Leukemia. 2002, 16 (7): 1381-9. 10.1038/sj.leu.2402512.View ArticlePubMedGoogle Scholar
- Rodeck U, Bossler A, Kari C, Humphreys CW, Gyorfi T, Maurer J, Thiel E, Menssen HD: Expression of the wt1 Wilms' tumor gene by normal and malignant human melanocytes. Int J Cancer. 1994, 59 (1): 78-82.View ArticlePubMedGoogle Scholar
- Viel A, Giannini F, Capozzi E, Canzonieri V, Scarabelli C, Gloghini A, Boiocchi M: Molecular mechanisms possibly affecting WT1 function in human ovarian tumors. Int J Cancer. 1994, 57 (4): 515-21.View ArticlePubMedGoogle Scholar
- Bergmann L, Miething C, Maurer U, Brieger J, Karakas T, Weidmann E, Hoelzer D: High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome. Blood. 1997, 90 (3): 1217-25.PubMedGoogle Scholar
- Hirose M: The role of Wilms' tumor genes. J Med Invest. 1999, 46 (3–4): 130-140.PubMedGoogle Scholar
- Zaia A, Fraizer GC, Piantanelli L, Saunders GF: Transcriptional regulation of the androgen signaling pathway by the Wilms' tumor suppressor gene WT1. Anticancer Res. 21 (1A): 1-10.Google Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/6/272/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.