References of "Sobel, Mark E"
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See detailMolecular Cloning of a Mutated Hoxb7 Cdna Encoding a Truncated Transactivating Homeodomain-Containing Protein
Chariot, Alain ULg; Senterre-Lesenfants, Sylviane; Sobel, Mark E et al

in Journal of Cellular Biochemistry (1998), 71(1), 46-54

Homeodomain-containing proteins regulate, as transcription factors, the coordinated expression of genes involved in development, differentiation, and malignant transformation. We report here the molecular ... [more ▼]

Homeodomain-containing proteins regulate, as transcription factors, the coordinated expression of genes involved in development, differentiation, and malignant transformation. We report here the molecular cloning of a mutated HOXB7 transcript encoding a truncated homeodomain-containing protein in MCF7 cells. This is a new example of mutation affecting the coding region of a HOX gene. In addition, we detected two HOXB7 transcripts in several breast cell lines and demonstrated that both normal and mutated alleles were expressed at the RNA level in MCF7 cells as well as in a variety of breast tissues and lymphocytes, suggesting that a truncated HOXB7 protein might be expressed in vivo. Using transient co-transfection experiments, we demonstrated that both HOXB7 proteins can activate transcription from a consensus HOX binding sequence in breast cancer cells. Our results provide evidence that HOXB7 protein has transcription factor activity in vivo and that the two last amino acids do not contribute to this property. [less ▲]

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See detailAntisense galectin-3 alters thymidine incorporation in human MDA-MB435 breast cancer cells
van den Brûle, Frédéric; Bellahcene, Akeila ULg; Jackers, Pascale ULg et al

in International Journal of Oncology (1997), 11(2), 261-264

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See detailIdentification of the active gene coding for the metastasis-associated 37LRP/p40 multifunctional protein.
Clausse, Nathalie; Jackers, Pascale ULg; Jares, P. et al

in DNA & Cell Biology (1996), 15(12), 1009-23

A 37LRP/p40 polypeptide is of major interest because it is consistently up-regulated in cancer cells in correlation with their invasive and metastatic phenotype. Furthermore, this polypeptide presents ... [more ▼]

A 37LRP/p40 polypeptide is of major interest because it is consistently up-regulated in cancer cells in correlation with their invasive and metastatic phenotype. Furthermore, this polypeptide presents intriguing multifunctional properties because it has been characterized as the precursor of the metastasis-associated 67-kD laminin receptor (67LR) and as a cytoplasmic ribosomal-associated protein. The isolation of the 37LRP/p40 gene is a prerequisite for identifying the molecular mechanisms responsible for the constant up-regulation of the 67LR expression in cancer cells. To date, the active 37LRP/p40 gene has never been identified in any species due to the existence of multiple pseudogenes in most vertebrates genomes. In this study, we report for the first time the gene structure and potential regulatory sequences of the 37 LRP/p40 gene. The chicken genome was selected to undergo this characterization because it is the only known vertebrate that bears a single 37 LRP/p40 gene copy. The 37 LRP/p40 active gene is composed of 7 exons and 6 introns and bears features characteristic of a ribosomal protein gene. It does not bear a classical TATA box and it exhibits several transcription initiation sites as demonstrated by RNase protection assay and primer extension. Analysis of potential regulatory regions suggests that gene expression is driven not only by the 5' genomic region but also by the 5' untranslated and intron 1 sequences. On the basis of gene structure and extensive protein evolutionary study, we found that the carboxyterminal domain of the protein is a conserved lock-and-key structure/function domain that could be involved in the biosynthesis of the higher-molecular-weight 67-kD laminin receptor in vertebrates, whereas the central core of the protein would be responsible for the ribosome associated function. The first identification of the active 37LRP/p40 gene presented in this study is a critical step toward the isolation of the corresponding human gene and the understanding of the molecular mechanisms involved in the up-regulation of its expression during tumor invasion and metastasis. [less ▲]

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See detailIsolation from a multigene family of the active human gene of the metastasis-associated multifunctional protein 37LRP/p40 at chromosome 3p21.3.
Jackers, Pascale ULg; Minoletti, Fabiola; Belotti, Dorina et al

in Oncogene (1996), 13(3), 495-503

The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose expression is consistently upregulated in aggressive carcinoma. Interestingly, the 37LRP appears to be a multifunctional ... [more ▼]

The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose expression is consistently upregulated in aggressive carcinoma. Interestingly, the 37LRP appears to be a multifunctional protein involved in the translational machinery and has also been identified as p40 ribosome-associated protein. Although highly conserved cDNAs corresponding to this polypeptide have been isolated from several species including vertebrates, invertebrates, plants and prokaryotes, characterization of any of the corresponding active genes has never been reported. In this study, we have cloned an intron-containing fragment which permitted us to isolate the active 37LRP/p40 human gene. This gene contains seven exons and six introns. Ribonuclease protection experiments suggest multiple transcription start sites. The promoter area does not bear a TATA box but contains four Sp1 sites. The first intron is also GC rich containing five Sp1 sites. Intron 4 contains the full sequence of the small nuclear RNA E2 and two Alu sequences are found in intron 3. Fluorescent in situ hybridization localized the 37LRP/p40 active gene on chromosome 3 in the locus 3p21.3 which, interestingly, is a hot spot for genetic alterations in several cancers and particularly in small cell lung carcinoma. [less ▲]

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See detailDecreased expression of galectin-3 is associated with progression of human breast cancer.
Castronovo, Vincenzo ULg; van den Brule, Frédéric; Jackers, Pascale ULg et al

in Journal of Pathology (The) (1996), 179(1), 43-48

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of ... [more ▼]

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in several biological events including binding to the basement membrane glycoprotein laminin. Although the exact role of galectin-3 during the interactions between cells and laminin is not yet known, it has recently been observed that its expression is down-regulated at both the protein and the mRNA level in colon cancer tissues in correlation with progression of the disease. This study investigated the possibility that breast cancer cells might also exhibit decreased galectin-3 expression in association with their aggressiveness. The expression of galectin-3 was examined by immunoperoxidase staining, using a polyclonal antibody raised against recombinant galectin-3, in a collection of 98 human breast lesions including 12 fibroadenomas, 15 fibrocystic disease lesions, 22 in situ carcinomas, and 49 infiltrating ductal carcinomas, 19 of which had positive axillary lymph nodes. Normal breast tissue adjacent to the lesions was present in 59 biopsies. Normal breast tissue expressed high levels (3+) of galectin-3. High expression (2+ to 3+) was also found in most benign lesions examined. The expression of galectin-3 was significantly decreased in in situ carcinoma and this down-regulation was more pronounced in invasive ductal carcinoma, particularly when associated with infiltration of axillary lymph nodes. These data constitute the first observation that galectin-3 is down-regulated in breast cancer and suggest the decreased expression of this galactoside-binding lectin is associated with the acquisition of the invasive and metastatic phenotype. [less ▲]

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See detailSeventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events
Jackers, Pascale ULg; Clausse, Nathalie; Fernandez, Maria-Teresa et al

in Biochimica et Biophysica Acta (1996), 1305(1-2), 98-104

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40 ... [more ▼]

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40). Interestingly, increased expression of this polypeptide (37LRP/p40) is consistently observed in invasive and metastatic cancer cells and is associated with poor prognosis. Southern-blot analysis of human genomic DNA predicted multiple copies of the 37LRP/p40 gene. In this study, we report that the number of copies of this sequence in the human genome is 26 +/- 2. We have sequenced and analyzed 19 genomic clones corresponding to the 37LRP/p40 gene and found that they were all processed pseudogenes. They all lack intronic sequences and show multiple genetic alterations leading in some cases to the appearance of stop codons. Moreover, they all bear characteristic features of retroposons as the presence of a poly(A)-tail at their 3' end and short direct repeated flanking DNA sequences. None of the pseudogenes analyzed present cis-elements in their 5' flanking region such as TATA or GC boxes. Our date reveal that over 50% of the 37LRP/p40 gene copies are pseudogenes most probably generated by retropositional events. The finding of multiple pseudogenes for the 37LRP/p40 suggests that the accumulation of several copies of this gene might have given a survival advantage to the cell in the course of evolution. [less ▲]

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See detailCloning and expression of a new HOXC6 transcript encoding a repressing protein
Chariot, Alain ULg; Castronovo, Vincenzo ULg; Le, P. et al

in Biochemical Journal (1996), 319

Homeodomain-containing proteins are transcription factors that regulate the co-ordinated expression of multiple genes involved in development, differentiation and malignant transformation. In an attempt ... [more ▼]

Homeodomain-containing proteins are transcription factors that regulate the co-ordinated expression of multiple genes involved in development, differentiation and malignant transformation. In an attempt to characterize expressed homeobox (HOX) genes in breast cancer cells, we cloned two distinct HOXC6 transcripts from an MCF7 cDNA library, Interestingly, one of them represents a new HOXC6 mRNA encoding a homeodomain-containing protein harbouring a unique N-terminal sequence. Moreover we demonstrate that this HOXC6 transcript is less abundant in human breast cancer cells than in non-tumorigenic cell lines, is detected in breast carcinomas and adjacent tissues and is expressed in a variety of human tumours. In addition, transient co-transfection experiments illustrated that both HOXC6 transcripts encode gene products that repress transcription from a HOX binding sequence in MDA-MB231 cells and co-operate with other HOX gene products such as HOXB7 on their target genes. Taken together, our results suggest that HOXC6 proteins might contribute to the breast cell phenotype through co-operative interactions with other HOX-derived proteins and repression of their target genes. [less ▲]

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See detailRetinoic Acid Induces Three Newly Cloned Hoxa1 Transcripts in Mcf7 Breast Cancer Cells
Chariot, Alain ULg; Moreau, Louis; Senterre, Geoffrey et al

in Biochemical and Biophysical Research Communications (1995), 215(2), 713-20

Coordinated expression of genes involved in development, differentiation and malignant transformation is regulated by transcription factors including homeodomain-containing proteins. However, most of ... [more ▼]

Coordinated expression of genes involved in development, differentiation and malignant transformation is regulated by transcription factors including homeodomain-containing proteins. However, most of their cDNA sequences are still unknown. We report here the molecular characterization of three newly cloned HOXA1 transcripts from human breast cancer cells. In addition, we provide evidence that these alternatively spliced transcripts encode one homeodomain-containing protein and two products lacking the conserved DNA-binding domain. Moreover, we demonstrate that all three HOXA1 transcripts are induced by retinoic acid in MCF7 cells. Taken together, our results suggest that HOXA1 gene may be a key element in the establishment of the breast cancer cell phenotype. [less ▲]

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