Ras responsive element binding protein‐1 (RREB‐1) down‐regulates hZIP1 expression in prostate cancer cells

Milon, Béatrice; Agyapong, Anthony A; Bautista, Roderick; Costello, Leslie C.; Franklin, Renty B.

doi:10.1002/pros.21063

Cited by 39 publications

(29 citation statements)

References 25 publications

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“…In addressing this important issue, we recently identified [46,47] that REBB-1 transcription factor (ras responsive binding element protein-1) is a negative regulator of ZIP1 gene expression (Fig. 10); and its in situ upregulation in early development of the malignant cells results in the down regulation of ZIP (Fig.…”

Section: The Zip1/zn Genetic/metabolic Transformation During the mentioning

confidence: 99%

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

Costello

Franklin

2016

Archives of Biochemistry and Biophysics

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The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely levels of citrate, which is achieved by the high cellular zinc level effects on the cell metabolism. This review highlights the specific functional and metabolic alterations that result from the accumulation of the high zinc levels, especially its effects on mitochondrial citrate metabolism and terminal oxidation. The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued.

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Section: The Zip1/zn Genetic/metabolic Transformation During the mentioning

confidence: 99%

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

Costello

Franklin

2016

Archives of Biochemistry and Biophysics

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193

180

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“…The membranes were stripped of antibody and re-probed with antiRREB1 and anti β-actin. 28 Statistical analysis was performed by a paired t test.…”

Section: Immunoblot (Western Blot)mentioning

confidence: 99%

The cytotoxic role of RREB1, ZIP3 zinc transporter, and zinc in human pancreatic adenocarcinoma

Franklin

Zou

Costello

2014

Cancer Biology & Therapy

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Pancreatic cancer (ductal adenocarcinoma) remains a deadly cancer with ~85% mortality, and a 5-year survival rate of ~6% or less for the past 30 years. The factors and events associated with the development of pancreatic cancer are poorly identified. As such, effective biomarkers for early detection of malignancy are lacking. Efficacious chemotherapy once the cancer is identified does not exist. Recent clinical studies have revealed that the zinc levels are consistently and markedly decreased in adenocarcinoma as compared with normal/benign pancreatic tissue. The decreased zinc is exhibited in well-differentiated malignancy and in progressing malignancy, and also exists throughout the development of PanIN. Concurrent with the decrease in zinc, RREB1 transcription factor and ZIP3 zinc uptake transporter are downregulated. Thus, a RREB1/ZIP3/Zinc transformation appears to be an early event in the development of pancreatic cancer. We propose that this transformation is necessary to prevent the accumulation of high cellular zinc levels, which result in cytotoxic effects on the developing malignant cells. This report now demonstrates that exposure of Panc1 cells to physiological concentrations of zinc that result in increased zinc uptake and accumulation also inhibits cell proliferation. The study further shows that ZIP3 is the important transporter required for the accumulation of zinc and its inhibition of proliferation. RREB1 is identified as the positive regulator of ZIP3 expression. Therefore, the pathway of RREB1/ZIP3/Zinc and its downregulation during oncogenesis exist to prevent the accumulation of cytotoxic levels of zinc during the development and progression of the malignant cells in pancreatic adenocarcinoma.

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“…The ability of RREB1 to increase transcription (15)(16)(17)(18) was not expected, since it lacks an intrinsic transcription activation domain (15) and was identified as a component of the multiprotein corepressor complex containing CtBP (19) and LSD1 (20). The majority of studies suggest a role for RREB1 in transcriptional repression of a number of genes (21)(22)(23)(24)(25)(26).…”

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confidence: 99%

CtBP and Associated LSD1 Are Required for Transcriptional Activation by NeuroD1 in Gastrointestinal Endocrine Cells

Ray

Metzger

et al. 2014

Molecular and Cellular Biology

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Gene expression programs required for differentiation depend on both DNA-bound transcription factors and surrounding histone modifications. Expression of the basic helix-loop-helix (bHLH) protein NeuroD1 is restricted to endocrine cells in the gastrointestinal (GI) tract, where it is important for endocrine differentiation. RREB1 (RAS-responsive element binding protein 1), identified as a component of the CtBP corepressor complex, binds to nearby DNA elements to associate with NeuroD and potentiate transcription of a NeuroD1 target gene. Transcriptional activation by RREB1 depends on recruitment of CtBP with its associated proteins, including LSD1, through its PXDLS motifs. The mechanism of transcriptional activation by CtBP has not been previously characterized. Here we found that activation was dependent on the histone H3 lysine 9 (H3K9) demethylase activity of LSD1, which removes repressive methyl marks from dimethylated H3K9 (H3K9Me2), to facilitate subsequent H3K9 acetylation by the NeuroD1-associated histone acetyltransferase, P300/CBP-associated factor (PCAF). The secretin, ␤-glucokinase, insulin I, and insulin II genes, four known direct targets of NeuroD1 in intestinal and pancreatic endocrine cells, all show similar promoter occupancy by CtBP-associated proteins and PCAF, with acetylation of H3K9. This work may indicate a mechanism for selective regulation of transcription by CtBP and LSD1 involving their association with specific transcription factors and cofactors to drive tissue-specific transcription.

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Ras responsive element binding protein‐1 (RREB‐1) down‐regulates hZIP1 expression in prostate cancer cells

Cited by 39 publications

References 25 publications

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer

The cytotoxic role of RREB1, ZIP3 zinc transporter, and zinc in human pancreatic adenocarcinoma

CtBP and Associated LSD1 Are Required for Transcriptional Activation by NeuroD1 in Gastrointestinal Endocrine Cells

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