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P Basset

Publications and source records attributed to P Basset.

At least 19 recordsLinked to original sources
PubMed1995

The cDNA cloning and expression of the gene encoding rat gelatinase B.

During a study aimed at defining the role of tissue remodeling genes implicated in wound healing, we isolated cDNA clones encoding gelatinase B (GelB) from a cDNA library derived from healing rat skin wound. The predicted rat GelB comprising 708 amino acids shows 75% and 82% identity with the human and mouse GelB, respectively. By Northern blot analysis, two GelB transcripts of 2.4 and 3.0 kb were observed in rat tissues, and shown to arise through the differential use of polyadenylation signals. Recombinant rat pro-GelB produced in transfected COS-1 cells exhibited a molecular weight of 92 kDa, as shown by gelatin zymography. Autocatalytic processing to active lower-molecular-weight forms was induced by 4-aminophenylmercuric acetate, and this process was inhibited in the presence of EDTA.

Amino Acid Sequence↗
PubMed1995

Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma.

CART1, a novel human gene, encodes a putative protein exhibiting three main structural domains: first, a cysteine-rich domain located at the amino-terminal part of the protein, which corresponds to an unusual RING finger motif; second, an original cysteine-rich domain located at the core of the protein and constituted by three repeats of an HC3HC3 consensus motif that we designated the CART motif, and which might interact with nucleic acid; third, the carboxyl-terminal part of the CART1 protein corresponds to a TRAF domain known to be involved in protein-protein interactions. Similar association of RING, CART, and TRAF domain was observed in the human CD40-binding protein and in the mouse tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), both involved in signal transduction mediated by the TNF receptor family and in the developmentally regulated Dictyostelium discoideum DG17 protein. CART1 is specifically expressed by epithelial cells in breast carcinomas and metastases. Moreover, in these malignant cells, the CART1 protein is localized in the nucleus. Altogether, these observations indicate that CART1 may be involved in TNF-related cytokine signal transduction in breast carcinoma.

Amino Acid Sequence↗
PubMed1995

Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the association of LIM and SH3 domains.

MLN 50 was previously identified in a cDNA library of breast cancer metastasis. In this study, we show that MLN 50, which is expressed at a basal level in normal tissues, is overexpressed in 8% of human breast carcinomas most often together with c-erbB-2. MLN 50 cDNA encodes a putative protein of 261 residues, named Lasp-1 (LIM and SH3 protein) since it contains a LIM motif and a domain of Src homology region 3 (SH3) at the amino- and the C-terminal parts of the protein, respectively. Thus, Lasp-1 defines a new LIM protein subfamily.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Comparative expression of the psoriasin (S100A7) and S100C genes in breast carcinoma and co-localization to human chromosome 1q21-q22.

Using differential screening of a breast cancer cDNA library, we isolated a cDNA encoding the psoriasin (S100A7) protein, previously identified in psoriatic epidermis. In the present study, we demonstrate that the psoriasin gene is expressed in breast cancer cell lines and in cancer cells of some breast carcinomas but not in any non-cancerous tissues examined, except skin. Another S100 gene, S100C, which we co-localized with the psoriasin gene to human chromosome 1q21-q22, was found to be expressed in most tissues and cell lines evaluated. These findings add support to the concept that the S100 genes clustered in human chromosome 1q21-q22 are individually controlled and that some of them may be involved in the regulation of cell transformation and/or differentiation.

Amino Acid Sequence↗
PubMed1995

Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities.

Matrix metalloproteinases (matrixins) constitute a group of extracellular proteinases belonging to the metzincin superfamily. They are involved in both physiological and pathological tissue remodeling processes, including those associated with cancer progression. Stromelysin-3, which is expressed in most invasive human carcinomas, is a matrix metalloproteinase with unusual functional properties. In particular, its mature form does not cleave any of the major extracellular matrix components. To define critical structural determinants involved in controlling stromelysin-3 proteolytic activity, we have used site-directed mutagenesis. We show that the deletion of at least 175 C-terminal amino-acids is sufficient to endow mouse stromelysin-3 with activities against casein, laminin, and type IV collagen. In the case of the human enzyme, however, a further and single Ala-235-->Pro substitution is necessary to observe similar activities. Ala-235, which characterizes human stromelysin-3 among matrixins, is located immediately after the C terminus of the "Met-turn," which forms a hydrophobic basis for the catalytic zinc atom in the metzincin family. We conclude that human stromelysin-3 has gained specific functional properties during evolution by amino acid substitution in the catalytic zinc environment, and that it represents an attractive target for specific inhibitors that may be used to prevent cancer progression.

Alanine↗
PubMed1995

Structure and promoter characterization of the human stromelysin-3 gene.

In the present study, we have isolated the human stromelysin-3 (ST3) gene which encodes a matrix metalloproteinase (MMP) expressed in fibroblastic cells of tissues associated with intense remodeling. The gene was found to span 11.5 kilobases (kb) including 8 exons and 7 introns. The genomic organization of ST3 gene exons is well conserved compared to other members of the MMP family, except for the 3 last exons corresponding to the hemopexin-like domain and to a long 3'-untranslated region. The transcription initiation site was located 31 nucleotides downstream of a TATA box. Analysis of 1.4 kb of 5'-flanking DNA sequence in the ST3 gene promoter revealed the presence of putative regulatory elements, but no consensus sequence for AP1-binding site in contrast to other MMP promoters. However, a specific cis-acting retinoic acid responsive element of the DR1 type was identified in the proximal region (-385) of the ST3 gene promoter. Transient transfection experiments demonstrated that a minimal promotor activity could be modulated by various sequences within the 3.4 kb of 5'-flanking region, and that the ST3 promoter was transactivated by retinoic acid receptors in the presence of retinoic acid. These findings indicate that the human ST3 gene promoter is characterized by structural and functional features which differ from those previously described in other MMP promoters, and further supports the possibility that ST3 gene expression is controlled by specific factors during tissue remodeling.

Animals↗
PubMed1995

Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17.

We have performed differential screening of a human metastatic lymph lymph node cDNA library to identify genes possibly involved during breast cancer progression. We have identified four novel genes overexpressed in malignant tiddues. They were all located on the long arm of chromosome 17, in loci located between q11 and q21.3, a region known to contain the c-erbB-2 oncogene and the BRCA1 breast carcinomas, and overexpression of three of them was dependent on gene amplification in breast cancer cell lines. These findings further support the concept that human chromosome 17 specifically carries genes possibly involved in breast cancer progression.

Adult↗
PubMed1995

A screening method to identify genes commonly overexpressed in carcinomas and the identification of a novel complementary DNA sequence.

We describe a differential screening method for cDNA libraries which used a combination of subtracted and PCR-amplified cDNA probes, and which can be applied to the selection of genes expressed in multiple tissues. This technique was used to identify genes commonly overexpressed in breast and basal cell carcinomas. These represent stromally dependent, invasive tumors with and without metastatic capacity. Thus, this screening sought to identify genes involved in the early stages of tumor progression. We identified a total of 16 genes, including c-erbB-2 and tissue inhibitor of metalloproteinases 3 whose products have been implicated in tumorigenesis or invasion. We also identified a novel sequence (D52) showing little homology with others described in any species, which maps to the human chromosomal band 8q21. In situ RNA hybridizations of breast carcinoma sections indicated that the D52 gene was expressed in cancer cells, whereas other genes identified in the differential screening were expressed in fibroblastic or inflammatory cells within the tumor stroma. Thus, the procedure developed in this study selected genes expressed in a diversity of cell types, indicating its potential usefulness in other systems.

Amino Acid Sequence↗
PubMed1995

Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas.

From breast cancer cDNA libraries, we have cloned cDNAs that proved to correspond to the membrane-type matrix metalloproteinase (MT-MMP) recently identified in human placenta and proposed to be an activator of progelatinase A [Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E. & Seiki, M. (1994) Nature (London) 370, 61-65]. Using one of these cDNAs as a probe, we have detected MT-MMP gene expression in all 83 human carcinoma specimens examined by RNA in situ hybridization and have found MT-MMP transcripts in fibroblastic cells of tumor stroma but not in cancer cells. Comparison with other MMP genes expressed in fibroblastic cells of human carcinomas indicated that the expression pattern of the MT-MMP gene was more closely related to that of the gelatinase A gene than to those of the stromelysin 3 or interstitial collagenase genes. These observations are consistent with the hypothesis that MT-MMP and gelatinase A are cooperating during tumor progression and strengthen the concept that proteolytic activities originating from the stromal component of human carcinomas have a critical role in tumor progression.

Adenocarcinoma↗
PubMed1995

Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin-3 and BM-40/SPARC genes.

The interaction of neoplastic cells with the extracellular matrix is a critical event for the initiation of cancer invasion and metastasis. This study was designed to evaluate the potential implication of stromelysin-3 (ST3), a newly identified member of the matrix-degrading metalloproteinase family, and of BM-40/SPARC, a glycoprotein associated with the extracellular matrix, during the progression of human colorectal cancers. We analyzed the relative abundance of ST3 and BM-40/SPARC transcripts by Northern blot, and their distribution by in situ hybridization, in normal mucosa, benign adenomas, and primary colorectal adenocarcinomas and their liver metastases. The ST3 and BM-40/SPARC transcripts were overexpressed in primary colorectal cancers and their liver metastases compared to non-neoplastic mucosa. These transcripts were localized in stromal fibroblasts adjacent to the neoplastic foci. Overexpression of ST3 correlated with the progression of human colorectal tumors toward local invasion and liver metastasis. Induction of these genes also occurred in diverticulitis and digestive neoplasms such as gastric and esophageal carcinomas.

Colorectal Neoplasms↗
PubMed1995

Developmental expression of mouse stromelysin-3 mRNA.

We have used northern blot analysis and in situ hybridization to study the spatial distribution of stromelysin-3 (ST3) expression during mouse embryogenesis. ST3 mRNA was observed in trophoblastic cells at the site of embryonic implantation (7.5-8.5 days) and in a variety of developing embryonic tissues. In these tissues, the highest ST3 expression levels were observed during the development of the external features of limb, tail and snout, and during bone and spinal cord morphogenesis. In limb, tail and snout, ST3 expression was specifically detected in mesenchymal cells lining the basement membrane at the junction of primitive dermis and epidermis, and adjacent to epithelial cells undergoing proliferation and/or apoptosis. In bone, ST3 was expressed in invasive mesenchymal cells and, in the spinal cord in neuroepithelial cells of the floor plate, at the time that this structure is crossed by commissural axons. Altogether, these observations suggest a role for ST3 during embryonic morphogenesis, in tissue remodeling processes associated with cell proliferation, death and/or invasion. Moreover, when compared to urokinase and tissue plasminogen activators, the spatiotemporal pattern of ST3 expression shows some similarities, but was not completely superimposable, suggesting that these genes may cooperate in some developing tissues and have specific functions in others.

Animals↗
PubMed1994

Cloning of the cDNA encoding rat tissue inhibitor of metalloproteinase 1 (TIMP-1), amino acid comparison with other TIMPs, and gene expression in rat tissues.

We have cloned the cDNA encoding the rat tissue inhibitor of metalloproteinase 1 (TIMP-1) from a cDNA library derived from healing skin wounds. The deduced amino acid (aa) sequence shows 66, 35 and 34% identity with human TIMP-1 and TIMP-2, and chicken TIMP-3 aa sequences, respectively. High-level expression of rat TIMP-1 RNA was detected in the skin wounds and in normal ovary.

Amino Acid Sequence↗
PubMed1994

Stromelysin-3 in stromal tissue as a control factor in breast cancer behavior.

BACKGROUND: It has long been proposed that secreted proteinases, including the matrix metalloproteinases, play an important part in tumor progression in mediating extracellular matrix remodeling. More recently, it has been suggested that extracellular proteinases also regulate growth factors and cytokines that may contribute to tumor progression. METHODS: RNA in situ hybridization and immunohistochemistry were used to study the expression, in breast and other types of human carcinomas, of the stromelysin-3 (ST3) gene, which encodes a putative new member of the matrix metalloproteinase family. RESULTS: The ST3 gene is overexpressed in most types of human carcinomas, including breast carcinoma where ST3 RNA was detected in 95% (99 of 104) of invasive primary tumors. Both ST3 protein and RNA are detected in fibroblastic cells immediately surrounding the cancer cells, but not in the malignant cells or in stromal cells at a distance from them. The ST3 gene also is expressed in some in situ breast carcinomas, where ST3 expression correlates with the known risk of these tumors to become invasive. CONCLUSIONS: ST3 is the paradigm of tumor proteinases that are not expressed in the malignant cells of human carcinomas but in fibroblastic cells of tumor stroma. ST3 represents a potential new prognostic parameter to identify subpopulations of aggressive tumors, particularly to evaluate the likelihood of in situ breast carcinoma progression to invasive cancer. Furthermore, the specific expression of the ST3 gene in fibroblastic cells immediately surrounding cancer cells suggests that ST3 may be involved in tumor progression and that it represents a potential target for cancer treatment.

Breast Neoplasms↗
PubMed1992

Assignment of the human stromelysin 3 (STMY3) gene to the q11.2 region of chromosome 22.

The human stromelysin 3 (STMY3) gene, a new member of the matrix metalloproteinase (MMP) gene family, may contribute to breast cancer cell invasion, and has been localized by in situ hybridization to the long arm of chromosome 22. As demonstrated using a panel of somatic cell hybrids, the STMY3 gene is in band 22q11.2, in close proximity to the BCR gene involved in chronic myeloid leukemia, but far from the (11;22) translocation breakpoint observed in Ewing sarcoma. This position differs from that reported on chromosomes 11 and 16 for the other MMP genes, suggesting that stromelysin 3 could be a member of a new MMP subfamily.

Breast Neoplasms↗
PubMed1992

The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis.

We have cloned from a mouse placenta cDNA library a mouse homologue of the human stromelysin-3 (ST3) cDNA, which codes for a putative matrix metalloproteinase expressed in breast carcinomas. The ST3 protein is well conserved between humans and mice, and the pattern of ST3 gene expression is similar in both species, and shows expression in the placenta, in the uterus, and during limb bud morphogenesis. We show that the ST3 gene can also be expressed in the normal mouse mammary gland. ST3 gene expression was not detected during mammary growth, neither in virgin nor in pregnant mice, but was specifically observed during postlactating involution of the gland, an apoptotic process associated with intense extracellular matrix remodeling. ST3 transcripts were found in fibroblasts immediately surrounding degenerative ducts, suggesting that ST3 gene expression may be associated with the basement membrane dissolution, which occurs during mammary gland involution. Since the ST3 gene is also specifically expressed in fibroblastic cells surrounding invasive neoplastic cells of breast carcinomas, we suggest that ST3 is implicated in extracellular matrix remodeling processes common to mammary apoptosis and breast cancer progression.

Amino Acid Sequence↗
PubMed1992

Breast-cancer-associated stromelysin-3 gene is expressed in basal cell carcinoma and during cutaneous wound healing.

Ten cases of basal cell carcinoma (BCC), including nine of the nodulo-ulcerative type and one of the morphea-form type, were investigated for stromelysin-3 (ST3) gene expression by in situ hybridization. The ST3 gene, which codes for a putative matrix metalloproteinase expressed in stromal cells of invasive breast carcinomas, was also expressed in stromal cells of BCCs when they displayed active local invasiveness. ST3 RNA was specifically detected in fibroblastic cells of tumor areas exhibiting loss of peripheral palisading in cancer cell islands. This pattern of expression was characteristic of the ST3 gene and was not observed with any of the other matrix metalloproteinase genes tested. We suggest that ST3 gene expression, which was also observed in fibroblasts during cutaneous scar formation, corresponds to a normal wound-healing response that has been subverted in carcinomas.

Breast Neoplasms↗
PubMed1988

Myelomonocytic cell lineage expression of the neutrophil elastase gene.

Human neutrophil elastase (NE) functions as a powerful serine protease capable of attacking a broad range of proteins. To examine the cellular site(s) of NE gene expression, a 0.65-kilobase cDNA (pPB15) complementary to the coding region of the NE gene was cloned from the cell line U937 using an oligonucleotide based on the known NE protein sequence. The sequence of pPB15 demonstrated that it coded for the 173 C-terminal residues of the 218 amino acids that comprise the mature NE protein, plus an additional 3' 60 base pairs prior to the in-frame stop codon, suggesting the NE mRNA contains sequences for a 20-residue C-terminal "pro" peptide that is not found in the mature protein. Northern analysis using 32P-labeled pPB15 as a probe revealed that neutrophils do not contain detectable NE mRNA transcripts despite the fact that this cell carries large amounts of this protein. Furthermore, resting and activated blood monocytes also contained no detectable NE mRNA transcripts, although these cells also carry detectable NE. In contrast, bone marrow precursor cells contained NE transcripts, suggesting the NE gene is expressed in blood precursor cells. In this regard, evaluation of HL-60 cells, a human cell line with myelomonocytic lineage features, demonstrated NE transcripts in resting cells and increased NE mRNA levels when the cells were induced toward the myelocytic lineage with dimethyl sulfoxide. However, when the HL-60 cells were induced toward the monocytic lineage with phorbol 12-myristate 13-acetate, NE transcripts were lost even though transcripts for interleukin-1 beta were plentiful. Together, these observations are consistent with the concept that the NE gene is not expressed in the blood cells that carry the protein, but in bone marrow precursors that express NE transcripts about the time of commitment to the myelocytic series.

Amino Acid Sequence↗