A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer

Perez‐Stable, Carlos; Pozas, Alicia de las; Roos, Bernard A.

doi:10.1016/s0303-7207(00)00300-2

Cited by 90 publications

(89 citation statements)

References 42 publications

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“…Although the transcription factor GATA-1 is considered to be specific of erythroid and megakaryocytic cells, a constitutively bound GATA-1 was identified in the DNA of the A549 lung tumour cell line (Richter et al, 2003), indicating that GATA-1 can be expressed in non hematopoietic cells. The prostate-specific antigen is a potential target gene for GATA transcription factors, but GATA-2 and -3 are the predominant GATA family members expressed in the prostate tissue (Perez-Stable et al, 2000). Here, we show the presence of the corresponding mRNA without detection of the protein in normal breast tissue, which could indicate a degradation of the transcription factor in normal conditions.…”

Section: Discussionmentioning

confidence: 68%

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

et al. 2010

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Expression of survivin, a member of the inhibitor of apoptosis protein family, is elevated in human cancers and considered as a new therapeutic target. Mechanism upregulating survivin expression in tumour cells is poorly understood. In this study, we show that breast cancer patients harbouring a polymorphism G235A in the survivin promoter present a higher level of survivin expression. This polymorphism creates a binding site for the transcription factor GATA-1 inducing a second GATA-1-binding site in survivin promoter. At the mRNA level, GATA-1 was present in breast carcinomas and adjacent normal tissues, whereas the protein was only detected in carcinomas by western blot and immunohistochemistry. Transfection of wild-type and different constitutively active GATA-1 mutants (serine 26, 178 or 310) showed that only phospho-serine 26 GATA-1 was able to increase survivin expression. This increase was higher in G235A than in G235G cell lines. Phospho-serine 26 GATA-1 bound directly survivin promoter, with a stronger interaction in G235A than in G235G polymorphism indicating that both GATA-1-binding sites are functional. These data identify GATA-1 as a key feature in tumour aggressiveness by enhancing survivin expression and delineate its targeting as a possible new therapeutic strategy in breast carcinomas.

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Section: Discussionmentioning

confidence: 68%

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

et al. 2010

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“…While we did not determine whether the GATA factors act directly on the PSA enhancer, it seems likely that they do, given the abundance of GATA sites in the PSA enhancer, their close juxtaposition with AREs (see Fig. S3 in the supplemental material), and a previous study demonstrating that the PSA enhancer binds to GATA factors in vitro (48). Further support for the generality of a collaboration between AR and GATA comes from a genome-wide study that found that the presence of consensus AREs near consensus GATA sites was a strong predictor that the AREs actually bound AR (42).…”

Section: Discussionmentioning

confidence: 93%

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

Bhardwaj

Rao

Kaur

et al. 2008

Molecular and Cellular Biology

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How Sertoli-specific expression is initiated is poorly understood. Here, we address this issue using the proximal promoter (Pp) from the Rhox5 homeobox gene. Its Sertoli cell-specific expression is achieved, in part, through a negative regulatory element that inhibits Pp transcription in non-Sertoli cell lines. Complementing this negative regulation is positive regulation conferred by four androgen-response elements (AREs) that interact with the androgen receptor (AR), a nuclear hormone receptor expressed at high levels in Sertoli cells. A third control mechanism is provided by a consensus GATA-binding site that is crucial for Pp transcription both in vitro and in vivo. Several lines of evidence suggested that GATA factors and AR act cooperatively to activate Pp transcription: (i) the GATA-binding site crucial for Pp transcription is in close proximity to two of the AREs, (ii) GATA and AR form a complex with the Pp in vitro, (iii) overexpression of GATA factors rescued expression from mutant Pp constructs harboring defective AREs, and (iv) incubation of a Sertoli cell line with testosterone triggered corecruitment of AR and GATA4 to the Pp. Collectively, our results suggest that the Rhox5 gene achieves Sertoli cell-specific transcription using a combinatorial strategy involving negative and cooperative positive regulation.

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“…1C). L6, LO, and R5 were reported previously as weak AR-binding sites, L4 as a strong AR-binding site (13), and L1 and L7 as GATA transcription factor-binding sites (14). In addition, the region that extends from R1 to R3 was also identified as the essential region for androgen-mediated PSA expression (Fig.…”

Section: Identification Of a Cluster Of Cis-elements Involved In Thementioning

confidence: 60%

“…In addition, six respective consensus GATA sites within this enhancer core, located on L7, L1, and R1 of the PSA enhancer core, have been proven to be essential for PSA gene expression (14). The cis-element responsible for the transcription activity of PSA enhancer core in the R1 region was GAGATA, instead of AGATAT, and the L7 region did not seem to contribute much to the PSA enhancer core activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel Transcription Factor, GAGATA-binding Protein, Involved in Androgen-mediated Expression of Prostate-specific Antigen

Wang

Yeung

Liu

et al. 2003

Journal of Biological Chemistry

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Prostate-specific antigen (PSA) is the most valuable marker for the evaluation of prostate cancer progression. The expression of PSA is controlled by androgen receptor (AR) through its binding to androgen-response elements (AREs). Several AREs have been identified within the 5.8-kb PSA promoter. The main activity of this 5.8-kb PSA promoter resides in a 455-bp enhancer core region located about 4 kb upstream of the TATA box. Our study suggests that in addition to the four AREs identified in the PSA enhancer core, another regulatory element (GAGATA), which is located at the region designated PSA3.1, also contributes to transcriptional regulation by androgens. Furthermore, electrophoretic mobility shift assay revealed that a putative transcriptional factor bound the GAGATA sequence in the PSA-producing prostate cancer cell. Further studies demonstrated that GAGATA factor preferentially bound the (G/C)(A/C/T)GATA sequence. The replacement of ATA with GGG in the GAGATA sequence completely eliminated the androgen-mediated transcriptional activity of the enhancer core. By using DNAcoupled magnetic beads and the Southwestern method, a 56 -60-kDa protein was identified as the putative GAGATA binding factor. EMSA and Western blotting assay suggested that AR is not involved in androgenmediated activation through PSA3

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A role for GATA transcription factors in the androgen regulation of the prostate-specific antigen gene enhancer

Cited by 90 publications

References 42 publications

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

The transcription factor GATA-1 is overexpressed in breast carcinomas and contributes to survivin upregulation via a promoter polymorphism

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

Identification of a Novel Transcription Factor, GAGATA-binding Protein, Involved in Androgen-mediated Expression of Prostate-specific Antigen

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