Biomedical subjects

C H Régnier

Publications and source records attributed to C H Régnier.

11 recordsLinked to original sources

PubMed1998

Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development.

This is the first in situ hybridization analysis of expression of a tumor necrosis factor (TNF) receptor associated factor (TRAF) during development. TRAF4 is observed throughout mouse embryogenesis, most notably during ontogenesis of the central (CNS) and peripheral (PNS) nervous system, and of nervous tissues of sensory organs. TRAF4 is preferentially expressed by post-mitotic undifferentiated neurons. Interestingly, TRAF4 remains expressed in the adult hippocampus and olfactory bulb, known to contain multipotential cells responsible for neoneurogenesis.

Amino Acid Sequence↗

PubMed1998

Expression of a truncated form of hHb1 hair keratin in human breast carcinomas.

Human hHb1 belongs to the type II hard keratin family and is physiologically expressed in hair shafts. In the present study, using specific 3' and 5' probes for hHb1, we established that breast carcinomas ectopically express a hHb1 5'-truncated mRNA, and that this transcript is restricted to malignant epithelial cells. Furthermore, an in vitro study indicated that it could be translated. We concluded that, in breast carcinomas, expression of truncated hHb1 is related to epithelial cell transformation. Because the hHb1 gene maps to 12q11-q13, a chromosome region known to present several breakpoints in solid tumours, we propose that the hHb1 gene might represent a target for such alterations.

Adult↗

PubMed1998

Lasp-1, a novel type of actin-binding protein accumulating in cell membrane extensions.

The Lasp-1 gene, which has been localized to the q12-q21 region of human chromosome 17, is amplified and overexpressed in human breast cancers. In addition to the previously reported LIM and SH3 domains of Lasp-1, we report here the identification of an actin-binding domain in the core of the protein. This domain is functional as we demonstrate that Lasp-1 binds actin in vivo and in vitro. In addition, confocal analysis of the Lasp-1 subcellular distribution shows that the protein is colocalized with actin at peripheral cell extensions in individual epithelial cancer cells and in transformed fibroblastic cells. Moreover, Lasp-1 is tyrosine phosphorylated in fibroblast cell lines transformed by a constitutively active form of c-Src (c-SrcY527F). Altogether, our results show that Lasp-1 defines a new type of actin-binding protein and suggest that the protein may play a role in a signaling pathway involved in the organization of the cytoskeleton.

3T3 Cells↗

PubMed1997

Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2.

TNF-induced activation of the transcription factor NF-kappaB and the c-jun N-terminal kinase (JNK/SAPK) requires TNF receptor-associated factor 2 (TRAF2). The NF-kappaB-inducing kinase (NIK) associates with TRAF2 and mediates TNF activation of NF-kappaB. Herein we show that NIK interacts with additional members of the TRAF family and that this interaction requires the conserved "WKI" motif within the TRAF domain. We also investigated the role of NIK in JNK activation by TNF. Whereas overexpression of NIK potently induced NF-kappaB activation, it failed to stimulate JNK activation. A kinase-inactive mutant of NIK was a dominant negative inhibitor of NF-kappaB activation but did not suppress TNF- or TRAF2-induced JNK activation. Thus, TRAF2 is the bifurcation point of two kinase cascades leading to activation of NF-kappaB and JNK, respectively.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1997

Identification and characterization of an IkappaB kinase.

Activation of the transcription factor NF-kappaB by tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the NF-kappaB-inducing kinase (NIK). In a yeast two-hybrid screen for NIK-interacting proteins, we have identified a protein kinase previously known as CHUK. Overexpression of CHUK activates a NF-kappaB-dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant-negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-kappaB activation. CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both serine 32 and serine 36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway. This phosphorylation of IkappaB-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated IkappaB-alpha kinase that links TNF- and IL-1-induced kinase cascades to NF-kappaB activation.

Cloning, Molecular↗

PubMed1997

MLN64 exhibits homology with the steroidogenic acute regulatory protein (STAR) and is over-expressed in human breast carcinomas.

The MLN64 gene, which is localized in q12-q21 of the human chromosome 17, encodes a novel protein containing 2 distinct domains. At the N-terminal, MLN64 exhibits a potential trans-membrane region, while at the C-terminal, it shares homology with the F26F4.4 protein of Coenorhabditis elegans and the steroidogenic acute regulatory (StAR) protein, a mitochondrial protein which is involved in steroid-hormone synthesis. By comparing the C-terminal part of these proteins, we defined a novel protein domain, which we termed SHD for "StAR Homology Domain". Of the 93 primary invasive breast carcinomas that were examined, 14 were found to over-express MLN64. These 14 tumors also expressed high c-erbB-2 transcript levels, which were not detected in the MLN64-negative tumors. MLN64 mRNA and protein were specifically detected in malignant cells of breast carcinomas. MLN64 protein was localized within bundle-like structures distributed throughout the cell cytoplasm and condensed in a perinuclear patch, suggesting an association with a specific cell compartment. When the N-terminal part of MLN64 was deleted, MLN64 was uniformly distributed in the cell cytoplasm, indicating that N-terminal part is involved in the specific cytoplasmic localization of MLN64. The homology between the C-terminal part of MLN64 and the functional StAR domain (SHD) suggests that MLN64 and StAR, although distributed in different cellular compartments, may both play a role in steroidogenesis. In this case, the high levels of MLN64 observed in some breast carcinomas could contribute to the progression of these tumors through increased intratumoral steroidogenesis.

Amino Acid Sequence↗

PubMed1997

Expression pattern of human hair keratin basic 1 (hHb1) in hair follicle and pilomatricoma.

Using in situ hybridization, human hair keratin basic 1 (hHb1) gene expression was investigated in human normal scalp. hHb1 transcripts were specifically detected in the cortical cells of hair shaft but neither in the outer and inner root sheaths, nor in the hair cuticle or the medulla. hHb1 expression was detected strongly in cortical cells located from the beginning of the keratogenous zone up to the isthmus. These data specify the localization of hHb1 expression. Furthermore, neoplasms with follicular differentiation, including trichoblastoma, trichoepithelioma, pilomatricoma, pilar carcinoma and basal-cell carcinoma, were analysed for hHb1 gene expression. One of the 4 pilomatricoma specimens examined exhibited a very high level of hHb1 transcripts. Interestingly, this labeling was specifically associated to a transitional cell layer en route to trichocytic differentiation, providing evidence that in pilomatricoma, epithelial germ cells can differentiate towards hair shaft keratinocytes before evolving in ghost cells.

Basal Cell Carcinoma↗

PubMed1996

Two distinct amplified regions at 17q11-q21 involved in human primary breast cancer.

Chromosomal segment 17q11-q21 is a commonly amplified region in human breast carcinomas. Several lines of evidence suggest that ERBB2 is the gene responsible for the emergence of this amplicon, but four novel genes (called MLN 50, MLN 51, MLN 62, and MLN 64) in 17q11-q21 have recently been found to be amplified and overexpressed in breast cancer cell lines. We investigated 98 primary breast tumors for amplification of these five loci. Twenty-five tumors (25.5%) showed amplification of at least one of these markers, but most amplifications did not encompass all of the tested loci. The genes most frequently amplified were ERBB2 and MLN 64 (22 of 25 amplified cases). MLN 64 was always coamplified with ERBB2, and to a similar level. Amplification of these five genes always leads to overexpression of their mRNA; we observed no cases of overexpression without amplification in any of these genes. Our results suggest that: (a) an independent, amplified region defined by MLN 62 (also called CART1 or TRAF4) is located in 17q11-q12; (b) in addition to ERBB2, MLN 64 is a major target for the 17q12-q21 amplicon; and (c) these MLN genes could be of pathogenetic significance in breast cancer.

Breast Neoplasms↗

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↗