Isolation and characterization of a novel gene induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver

Selmin, Ornella I.; Lucier, George W.; Clark, Georgina J.; Tritscher, Angelika; Vandenheuvel, J; Gastel, Jonathan A.; Walker, Nigel J.; Sutter, Thomas R.; Bell, David

doi:10.1016/s0928-4346(97)89848-9

Cited by 36 publications

(74 citation statements)

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“…The sequence was found to be consistent with that of a protein reported previously as '25-Dx' (GenBank accession number U63315) [9] or 'membrane-associated progesterone receptor (MPR)' (GenBank accession number AJ005837) [10]. In the human genome sequence, two genes encode IZA; one, Hpr6.6 (accession number NM_006667), encodes a protein corresponding to rIZA1, which we name here hIZA1, and the other, Dg6 (accession number NM_006320), encodes a protein similar to, although distinctly different from, the protein named hIZA2 here [11].…”

supporting

confidence: 80%

Molecular identification of adrenal inner zone antigen as a heme‐binding protein

et al. 2005

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The adrenal inner zone antigen (IZA), which reacts specifically with a monoclonal antibody raised against the fasciculata and reticularis zones of the rat adrenal, was previously found to be identical with a protein variously named 25‐Dx and membrane‐associated progesterone receptor. IZA was purified as a glutathione S‐transferase‐fused or His6‐fused protein, and its molecular properties were studied. The UV‐visible absorption and EPR spectra of the purified protein showed that IZA bound a heme chromophore in high‐spin type. Analysis of the heme indicated that it is of the b type. Site‐directed mutagenesis studies were performed to identify the amino‐acid residues that bind the heme to the protein. The results suggest that two Tyr residues, Tyr107 and Tyr113, and a peptide stretch, D99–K102, were important for anchoring the heme into a hydrophobic pocket. The effect of IZA on the steroid 21‐hydroxylation reaction was investigated in COS‐7 cell expression systems. The results suggest that the coexistence of IZA with CYP21 enhances 21‐hydroxylase activity.

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supporting

confidence: 80%

Molecular identification of adrenal inner zone antigen as a heme‐binding protein

et al. 2005

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“…The rat analog of the porcine progesterone binding membrane protein (mPR), 25-Dx (436), has been shown to be expressed to a higher level in female PR KO mice than in their wild-type cognates (238). Together with other data on the regulation of its expression, a mechanism has been suggested by which 25-Dx expression is repressed through activated PR, which shares some similarities with regulation in the case of aldosterone.…”

Section: Knock-out Micementioning

confidence: 97%

“…Interestingly, the rat equivalent of mPR, termed 25-Dx (436), has been associated with behavioral processes. In the ventromedial hypothalamus of rats, 25-Dx expression has been shown to be repressed by progesterone after estradiol priming of ovariectomized animals.…”

Section: Progesteronementioning

confidence: 99%

Nongenomic Steroid Action: Controversies, Questions, and Answers

Lösel

Falkenstein

Feuring

et al. 2003

Physiological Reviews

500

320

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Lösel, Ralf M., Elisabeth Falkenstein, Martin Feuring, Armin Schultz, Hanns-Christian Tillmann, Karin Rossol-Haseroth, and Martin Wehling. Nongenomic Steroid Action: Controversies, Questions, and Answers. Physiol Rev 83: 965–1016, 2003; 10.1152/physrev.00003.2003.—Steroids may exert their action in living cells by several ways: 1) the well-known genomic pathway, involving hormone binding to cytosolic (classic) receptors and subsequent modulation of gene expression followed by protein synthesis. 2) Alternatively, pathways are operating that do not act on the genome, therefore indicating nongenomic action. Although it is comparatively easy to confirm the nongenomic nature of a particular phenomenon observed, e.g., by using inhibitors of transcription or translation, considerable controversy exists about the identity of receptors that mediate these responses. Many different approaches have been employed to answer this question, including pharmacology, knock-out animals, and numerous biochemical studies. Evidence is presented for and against both the participation of classic receptors, or proteins closely related to them, as well as for the involvement of yet poorly understood, novel membrane steroid receptors. In addition, clinical implications for a wide array of nongenomic steroid actions are outlined.

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“…Pgrmc1 is overexpressed in multiple types of cancer, including breast, thyroid, colon, ovary, and lung cancer (Rohe et al, 2009), and Pgrmc1 levels correlate with tumor stage in ovarian cancer (Peluso et al, 2008a) and estrogen receptor status in breast cancer (Craven, 2008;Neubauer et al, 2008). Pgrmc1 is also induced during dioxin-stimulated tumorigenesis (Selmin et al, 1996) and is part of a six-gene signature associated with nongenotoxic carcinogens (Nie et al, 2006). Pgrmc1 promotes survival in cancer cells (Peluso et al, 2006(Peluso et al, , 2008b, particularly in response to chemotherapeutic drugs (Crudden et al, 2006;Peluso et al, 2008a), and the Pgrmc1 yeast homolog, called Dap1, is also required for damage-dependent survival (Rohe et al, 2009).…”

mentioning

confidence: 99%

Progesterone Receptor Membrane Component 1 (Pgrmc1): A Heme-1 Domain Protein That Promotes Tumorigenesis and Is Inhibited by a Small Molecule

Ahmed

Rohe²,

Twist³

et al. 2010

J Pharmacol Exp Ther

131

149

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Tumorigenesis requires the concerted action of multiple pathways, including pathways that stimulate proliferation and increase metabolism. Progesterone receptor membrane component 1 (Pgrmc1) is related to cytochrome b 5 , binds to heme, and is associated with DNA damage resistance and apoptotic suppression. Pgrmc1 is induced by carcinogens, including dioxin, and is up-regulated in multiple types of cancer. In the present study, we found that Pgrmc1 increased in vivo tumor growth, anchorage-independent growth, and migration. Pgrmc1 also promoted proliferation in the absence of serum in A549 non-small cell lung cancer cells but enhanced proliferation regardless of serum concentration in MDA-MB-468 breast cancer cells. Pgrmc1 promotes cholesterol synthesis and binds to Insig (insulininduced gene), Scap (sterol regulatory element binding protein cleavage activating protein), and P450 proteins, but Pgrmc1 did not affect cholesterol synthesis in lung cancer cells. Pgrmc1 is also associated with progesterone signaling and plasminogen activator inhibitor (PAI1) RNA binding protein, but neither progesterone activity nor PAI1 transcript levels were altered in Pgrmc1-knockdown lung cancer cells. Pgrmc1 homologues bind to aryl ligands identified in an in silico screen, and we have found that a Pgrmc1 ligand induced cell death in a Pgrmc1-specific manner in multiple breast and lung tumor cell lines. Our data support a role for Pgrmc1 in promoting cancer-associated phenotypes and provide a therapeutic approach for targeting Pgrmc1 with a small molecule in lung and breast cancer.

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Isolation and characterization of a novel gene induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver

Cited by 36 publications

References 0 publications

Molecular identification of adrenal inner zone antigen as a heme‐binding protein

Molecular identification of adrenal inner zone antigen as a heme‐binding protein

Nongenomic Steroid Action: Controversies, Questions, and Answers

Progesterone Receptor Membrane Component 1 (Pgrmc1): A Heme-1 Domain Protein That Promotes Tumorigenesis and Is Inhibited by a Small Molecule

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