Regulated expression of the Ren-2 gene in transgenic mice derived from parental strains carrying only the Ren-1 gene.

Tronik, Diana; Dreyfus, Marc; Babinet, C.; Rougeon, François

doi:10.1002/j.1460-2075.1987.tb04848.x

Cited by 74 publications

(21 citation statements)

References 33 publications

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“…Since the cath-D gene is controlled by a mixed promoter, this gene has the advantage of being both constitutively expressed from TATA-independent start sites and overexpressed in some physiological ( (25) and renin, which is also regulated by a steroid (26). The only known example of a dual promoter with multiple start sites is the metallothionein-I gene, in which initiation involving the TATA box is facilitated by heavy metal inducers and varies according to the tissue (27).…”

Section: Resultsmentioning

confidence: 99%

Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells.

Cavaillès

Augereau

Rochefort

1993

Proc. Natl. Acad. Sci. U.S.A.

139

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The cathepsin D (cath-D) gene, coding for a ubiquitous Iysosomal aspartyl protease, is overexpressed in aggressive human breast cancers, and its transcription is induced by estrogens in hormone-responsive breast cancer cells. We have determined the structure and function of the proximal 5' upstream region of the human cath-D gene from MCF7 cells. We show that the promoter has a compound structure with features of both housekeeping genes (high G+C content and potential transcription factor Spl sites) and regulated genes (TATAA sequence). By RNase protection assay, we show that transcription is initiated at five major transcription sites (TSSI to -V) spanning 52 base pairs. In hormoneresponsive breast cancer cells, estradiol increased by 6-to 10-fold the level of RNAs initiated at TSSI, which is located about 28 base pairs downstream from the TATA box. The specific regulation by estradiol of transcription starting at site I exclusively was confimed by primer extension. Moreover, the same estradiol effect was observed in the ZR75-1 cell line and in MDA-Ml231 estrogen-resistant breast cancer cells stably transfecte4 with the estrogen receptor. Site-directed mutagenesis in,#1c!Ited that the TATA box is essential for initiation ofcatfll') gene transcription at TSSI. In breast cancer biopsy samples, high levels of TATA-dependent transcription were correlated with overexpression of cath-D mRNA. We conclude that cath-D behaves, depending on the conditions, as a housekeeping gene with multiple start sites or as a hormoneregulated gene that can be controlled from its TATA box.Steroid repeptors increase the initiation of transcription of specific geneX lay interacting with the transcriptional machinery at thy promoter level (1). Cathepsin D (cath-D), a lysosomal gspartyl protease, is induced by estrogens in human breast cancer cell lines (2) and is produced in excess in cancer cells both in vitro and in vivo, where its concentration in the primary tumor is correlated with increased risk of metastasis (for review see ref.3).In eukaryotes, gene expression is controlled by both proximal and distal elements, generally located in the 5' upstream region of the gene (4). Many class II gene promoters contain a TATA box, which binds the transcription factor IID and defines the transcription initiation site; genes with these promoters have been called facultative or regulated genes. In contrast, promoters of housekeeping genes, such as those coding for lysosomal enzymes (5), lack a recognizable TATA box but contain multiple GC boxes acting as putative binding sites for the transcription factor Spl (6).We have previously shown, in human breast cancer cell lines, that estrogens stimulate transcription of the cath-D gene by means of estrogen-responsive sequences located in the proximal region of the promoter (7). Here we show, using RNase protection and primer extension, that cath-D gene transcription in breast cancer cells is initiated at multiple sites by a mixed promoter having characteristics of the promoters of both houseke...

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Section: Resultsmentioning

confidence: 99%

Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells.

Cavaillès

Augereau

Rochefort

1993

Proc. Natl. Acad. Sci. U.S.A.

139

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“…Preparation of RNA-Total RNA was isolated from sublingual (SLG) and submaxillary (SMG) salivary glands and from liver according to Chirgwin's protocol (21), modified as described previously (22,23).…”

Section: Methodsmentioning

confidence: 99%

cDNA Cloning and Sequencing Reveal the Major Horse Allergen Equ c1 to Be a Glycoprotein Member of the Lipocalin Superfamily

Grégoire¹,

Rosinski‐Chupin

Rabillon³

et al. 1996

Journal of Biological Chemistry

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The gene encoding the major horse allergen, designated Equus caballus allergen 1 (Equ c1), was cloned from total cDNA of sublingual salivary glands by reverse transcription-polymerase chain reaction using synthetic degenerate oligonucleotides deduced from N-terminal and internal peptide sequences of the glycosylated hair dandruff protein. A recombinant form of the protein, with a polyhistidine tail, was expressed in Escherichia coli and purified by immobilized metal affinity chromatography. The recombinant protein is able to induce a passive cutaneous anaphylaxis reaction in rat, and it behaves similarly to the native Equ c1 in several immunological tests with allergic patients' IgE antibodies, mouse monoclonal antibodies, or rabbit polyclonal IgG antibodies. Amino acid sequence identity of 49 -51% with rodent urinary proteins from mice and rats suggests that Equ c1 is a new member of the lipocalin superfamily of hydrophobic ligand-binding proteins that includes several other major allergens. An RNA blot analysis demonstrates the expression of mRNA Equ c1 in liver and in sublingual and submaxillary salivary glands.

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“…RNA was prepared from mouse and rat tissues as described (8). In vitro translation of RNAs was performed with the mRNAdependent reticulocyte lysate translation system (9).…”

Section: Methodsmentioning

confidence: 99%

High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

Rosinski‐Chupin

Tronik

Rougeon

1988

Proc. Natl. Acad. Sci. U.S.A.

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NaDodSO4/PAGE analysis of in vitro translation products of rat submaxillary gland (SMG) mRNAs has revealed an important sexual dimorphism. Moreover, most of the rat male-specific major translation products differ in size from those translated from male mouse SMG mRNAs. To characterize proteins accumulated in the rat SMG under androgen control, a cDNA library was constructed. Here we report the nucleotide sequence of a 0.7-kilobase mRNA that is 1000-3000 times more abundant in male rats than in female rats. The predicted corresponding protein, SMR1, has a molecular weight of 16,000 and contains a signal peptide for secretion and potential signals for glycosylation. An interesting feature of SMR1 is the presence, in a hydrophilic region, of the tetrapeptide Gln-His-Asn-Pro surrounded by two pairs of basic residues that represent potential cleavage sites for maturation enzymes. In rats, the tissue distribution of the SMR1 mRNA is restricted to the SMG and the prostate. Only very low amounts of SMR1 mRNA can be detected in the SMG of male or female mice. Southern blot analysis indicates the presence of three genes in rats but only one in mice. Hypotheses on the physiological role of SMR1-derived peptides in male rats are discussed.A large number of polypeptides with biologically defined properties are synthesized at high levels in the submaxillary gland (SMG) of rodents (1) and particularly of mice. These proteins, including nerve growth factor (NGF), epidermal growth factor (EGF), and renin, share a number of properties. All are synthesized in the same cell type-the granular convoluted tubular (GCT) cells-in response to various hormonal stimuli, in particular to androgens (2). Further, these secretory proteins can be found in the saliva of mice and are synthesized as precursors that become active after posttranslational processing events, possibly involving kallikrein-like proteinases. Some of these kallikrein-like proteinases are also synthesized under androgen-control in the SMG (3).The biological significance of the accumulation of these polypeptides in the SMG of mice and of their release into the saliva is still unclear. Aggressive behavior in male mice results in the release into the blood of large amounts of submaxillary NGF and renin (4,5), providing some evidence that these molecules play a physiological role. But surprisingly, these proteins are not detected in the SMG of related species. For instance, renin, which represents 2% of the SMG proteins in wild-type and most inbred male mice (6) is not found in the SMG of rats (7). This suggests that these SMG-synthesized polypeptides could be related to the especially aggressive behavior of male mice.Attempts to characterize the genes regulated by androgens in the SMG of rats led us to analyze the patterns of in vitro translation products directed by the mRNAs of this tissue. As in mice, an important sexual dimorphism was observed in the rat SMG translation products. Moreover, the major polypeptides accumulated in the two species appeared to be very ...

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Regulated expression of the Ren-2 gene in transgenic mice derived from parental strains carrying only the Ren-1 gene.

Cited by 74 publications

References 33 publications

Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells.

Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells.

cDNA Cloning and Sequencing Reveal the Major Horse Allergen Equ c1 to Be a Glycoprotein Member of the Lipocalin Superfamily

High level of accumulation of a mRNA coding for a precursor-like protein in the submaxillary gland of male rats.

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