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Titolo:
Transcriptional regulation of the androgen signaling pathway by the Wilms'tumor suppressor gene WT1
Autore:
Zaia, A; Fraizer, GC; Piantanelli, L; Saunders, GF;
Indirizzi:
Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 Biochem & Mol Biol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 anc Ctr, Dept Urol, Houston, TX 77030 USA INRCA, Ctr Biochem, Gerontol & Geriatr Res Dept, I-60100 Ancona, Italy INRCA Ancona Italy I-60100 tol & Geriatr Res Dept, I-60100 Ancona, Italy
Titolo Testata:
ANTICANCER RESEARCH
fascicolo: 1A, volume: 21, anno: 2001,
pagine: 1 - 10
SICI:
0250-7005(200101/02)21:1A<1:TROTAS>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR MESSENGER-RNA; DNA-BINDING SPECIFICITY; GROWTH-FACTOR RECEPTORS; FACTOR-I; RESPONSE ELEMENT; STEROID-HORMONES; PROSTATIC GROWTH; CELL-LINES; EXPRESSION; REPRESSION;
Keywords:
androgen-signaling pathway; androgen receptor; Wilms' tumor suppressor gene; prostate cancer cell lines;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Saunders, GF Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, 1515 Holcombe Blvd,Box 117, Houston, TX 77030 USA Univ Texas 1515 Holcombe Blvd,Box 117 Houston TX USA 77030 SA
Citazione:
A. Zaia et al., "Transcriptional regulation of the androgen signaling pathway by the Wilms'tumor suppressor gene WT1", ANTICANC R, 21(1A), 2001, pp. 1-10

Abstract

The androgen-signaling pathway plays a critical role in prostate cancer development and progression. We have recently demonstrated that the Wilms' tumor suppressor gene product, WT1, binds to multiple sites in the androgen receptor (AR) promoter and transcriptionally represses the AR gene promoter in vitro. We asked whether WT1 repression of the endogenous AR gene interferes in the androgen signal transduction cascade and modifies AR target geneexpression. We analyzed the effect of WT1 (-/-) overexpression on an AR target gene reporter construct that contains the luciferase gene, the ElB TATA box, and two copies of the androgen- respnose element (ARE), the dimeric AR binding site. Luciferase activity was determined in 293 kidney and TM4 Sertoli cells, two nontumorigenic cell lines that express both AR and WT1. Cells were cotransfected by lipofectamine in the presence or absence of the synthefic androgen R1881. Results showed that the overexpression of WT1 downregulates ARE-reporter gene transcription in both cell lines tested. the inhibitory effect of WT1 on the AR target gene construct was dose- dependentand androgen-independent in 293 cells, whereasin TM4 cells it was androgen-dependent. Additionally, a zinc-finger mutant WT1(-/-) expression construct, R394W, failed to decrease luciferase activity, suggesting that WT1 downregulates the ARE-reporter gene construct activity by directly repressing the endogenous AR gene promoter. Furthermore, we analyzed the expression of WT1 and AR mRNA in several prostate cancer cell lines in order to understandthe role WT1 may play in prostate cancer development and progression. Gel analysis of cDNA amplified by RT-PCR of AR and WT1 RNA from prostate cancerand non- prostatic cell lines showed that LNCaP and MDAPCa2b, two metastatic prostate cancer cell lines which are androgen-sensitive, expressed AR but not WT1. Du145 and Pc3, two cell lines from advanced metastatic prostate cancer, which are characterized as androgen-independent and -insensitive, did not express AR but expressed a high level of WT1. Two non-prostatic celllines, T47D and 293, weakly co-expressed AR and WT1. This inverse relationship between AR and WT1 expression in prostate cancer cell lines, together with WT1 repression of the AR promoter, suggest a role for WTI in the androgen signaling pathway and in prostate cancer development and progression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 14:45:36