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

Cavaillès, Vincent; Augereau, Patrick; Rochefort, Henri

doi:10.1073/pnas.90.1.203

Cited by 139 publications

(100 citation statements)

References 32 publications

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“…Because cathepsin D misregulation is implicated in cancer progression (reviewed by Fusek and Vetvicka, 2005;Liaudet-Coopman et al, 2006), altering hSPE-39 levels in vivo may have important consequences. Cathepsin D expression in estrogen receptor-positive breast cancer cells is regulated by estrogen (Cavailles et al, 1993), and a recent study indicates that the hSPE-39 promoter binds estrogen receptor ␣ in a hormone-dependent manner (Laganiere et al, 2005). This suggests that hSPE-39 plays an important role in cathepsin D regulation in vivo.…”

Section: Discussionmentioning

confidence: 92%

SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery

Zhu

Salazar²,

Zlatic³

et al. 2009

MBoC

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Yeast and animal homotypic fusion and vacuole protein sorting (HOPS) complexes contain conserved subunits, but HOPS-mediated traffic in animals might require additional proteins. Here, we demonstrate that SPE-39 homologues, which are found only in animals, are present in RAB5-, RAB7-, and RAB11-positive endosomes where they play a conserved role in lysosomal delivery and probably function via their interaction with the core HOPS complex. Although Caenorhabditis elegans spe-39 mutants were initially identified as having abnormal vesicular biogenesis during spermatogenesis, we show that these mutants also have disrupted processing of endocytosed proteins in oocytes and coelomocytes. C. elegans SPE-39 interacts in vitro with both VPS33A and VPS33B, whereas RNA interference of VPS33B causes spe-39-like spermatogenesis defects. The human SPE-39 orthologue C14orf133 also interacts with VPS33 homologues and both coimmunoprecipitates and cosediments with other HOPS subunits. SPE-39 knockdown in cultured human cells altered the morphology of syntaxin 7-, syntaxin 8-, and syntaxin 13-positive endosomes. These effects occurred concomitantly with delayed mannose 6-phosphate receptor-mediated cathepsin D delivery and degradation of internalized epidermal growth factor receptors. Our findings establish that SPE-39 proteins are a previously unrecognized regulator of lysosomal delivery and that C. elegans spermatogenesis is an experimental system useful for identifying conserved regulators of metazoan lysosomal biogenesis. INTRODUCTIONLysosome biogenesis is mediated by multiple vesicular budding and fusion events that deliver components between subcellular compartments (Luzio et al., 2003). In Saccharomyces cerevisiae, vesicular fusion at the vacuole (the yeast equivalent of lysosomes) requires the homotypic fusion and vacuole protein sorting (HOPS) complex, which regulates vesicle docking through its interaction with soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (SNAREs) and the Rab protein Ypt7p Sato et al., 2000;Wurmser et al., 2000). The yeast HOPS complex contains class C Vps proteins Vps11p, Vps16p, Vps18p, and Vps33p (Rieder and Emr, 1997) and class B Vps proteins Vps39p and Vps41p (Seals et al., 2000;Wurmser et al., 2000). In addition to vesicular fusion at the vacuole, the class C Vps proteins also function in Golgi-to-endosome transport and other steps in vacuolar delivery pathways (Srivastava et al., 2000;Peterson and Emr, 2001;Subramanian et al., 2004;Peplowska et al., 2007). Involvement of the class C Vps proteins at multiple stages has also been reported in mammalian cells (Kim et al., 2003;Richardson et al., 2004). Vesicular trafficking to the lysosome has been extensively described in yeast (Bowers and Stevens, 2005), but it is also known that this process is more complex in metazoans (Dell'Angelica, 2004). Yeast only has lysosomes of a single type, whereas animals have lysosomes and lysosome-related organelles that are functionally diverse. This diversity is evident when comparing th...

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Section: Discussionmentioning

confidence: 92%

SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery

Zhu

Salazar²,

Zlatic³

et al. 2009

MBoC

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“…A mixed promoter controls the cathepsin D gene, and estrogens stimulate only the TATA-dependent transcription in breast cancer cells (Cavailles et al, 1993). The promoter region of the cathepsin D gene does not contain a canonical ERE palindrome (Augereau et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines

et al. 1999

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We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identi®cation of two important control regions, one in pS2 and the other in cathepsin D genes. In the hormonedependent MCF7 cell line, within the pS2 gene 5'-anking region, we detected two major DNase I hypersensitive sites, induced by estrogens and/or IGFI: pS2-HS1, located in the proximal promoter and pS2-HS4, located 710.5 Kb from the CAP site, within a region that has not been cloned. The presence of these two DNase I hypersensitive sites correlates with pS2 expression. Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable chromatin structural changes over the pS2 regulatory region, suggesting that the two transduction-pathways converge to a unique chromatin target. In two cell lines that do not express pS2, MDA MB 231, a hormone-independent cell line that lacks the estrogen receptor a, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor a, there was only one hormoneindependent DNase I hypersensitive site. This site, pS2-HS2, was located immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive sites were present in the 5'-¯anking sequences of the cathepsin D gene, which is regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3, located at positions 72.3 Kb and 73.45 Kb, respectively, were both hormone-independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA MB 231 cells, that express cathepsin D constitutively, we detected an additional strong hormoneindependent DNase I hypersensitive site, catD-HS4, located at position 74.3 Kb. This region might control the constitutive over-expression of cathepsin D in hormone-independent breast cancer cells. All together, these data demonstrate that a local reorganization of the chromatin structure over pS2 and cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells.

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“…21 The mechanism of regulation of expression has been studied extensively and DNA sequences responsible for this regulation have been determined. 19,22 A strong predictive value was found for CD concentrations in breast cancer as well as many other tumor types. 15,23,24 Subsequently, it has been recommended that levels of CD be monitored as a prognostic indicator in breast cancer and used independent of classical prognostic parameters such as tumor size, histological grade, lymph node status, and steroid receptor expression.…”

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confidence: 97%

“…Progesterone and its derivatives increase the rate of uterine CD synthesis, 17 and in breast cancer cell lines, CD expression is regulated by estrogens 18 that interact at the promoter level. 19 In ER + cell lines, pCD is secreted only after estrogen stimulation. The estrogen stimulation of pCD secretion from breast cancer cells can be specifically inhibited by a specific estrogen inhibitor 2,3,7,8-tetrachlorodibenzo-p-dioxin.…”

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confidence: 99%

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

2002

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Procathepsin D (pCD) is a major secreted glycoprotein in some human breast and other cancer cell lines. Several groups proposed that pCD served as a growth factor for these cell lines. Secreted pCD has been demonstrated in tissue section, tissue culture supernatants, carcinoma cytosols, and nipple aspirates. Moreover, several clinical studies suggested a potential role for this molecule in metastasis because its concentration in primary tumors correlated with an increased incidence of tumor metastases. In this paper, the effects of pCD were evaluated by proliferation in vitro and by mouse studies in vivo. Subsequent flow cytometry experiments showed the specificity of pCD binding to cancer cells. Cell cultivation showed that addition of either pCD or its activation peptide stimulates growth of cancer cells. These effects can be inhibited both in vitro and in vivo by anti-pCD antibodies. In addition, production of pCD can be inhibited by specifically designed ribozymes. This paper is focused on mitogenic effects of pCD, which seem to involve interaction of the activation peptide with as yet unidentified receptor. Different mechanisms by which pCD could promote development and spread of cancer cells are discussed.

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

Cited by 139 publications

References 32 publications

SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery

SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery

Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines

Procathepsin D in breast cancer: What do we know? Effects of ribozymes and other inhibitors

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