Biomedical subjects

Bernard Perbal

Publications and source records attributed to Bernard Perbal.

26 records · Page 2Linked to original sources

PubMed2003

Deletions within the U3 long terminal repeat alter the tumorigenic potential of myeloblastosis associated virus type 1(N).

The molecularly cloned myeloblastosis-associated virus type-1(N) (MAV-1(N)) strain induces specifically nephroblastomas in chicken. MAV-induced nephroblastoma constitutes a unique animal model of the human Wilms' tumor. We have previously shown that the MAV-1(N) long terminal repeats (LTR) were necessary and sufficient for nephroblastoma induction. Since major determinants for oncogenesis have been mapped in the U3 region of several other retroviruses, we have analyzed the tumorigenic potential of five recombinant viruses partially deleted in their U3 region. The results obtained indicated that deletions of the LTRs resulted in a modification of the pathogenic spectrum of MAV-1(N) and a decreased efficiency for nephroblastoma induction.

Animals↗

PubMed2003

Communication is the key.

All forms of communication between human beings have long been recognized as a requirement for reciprocal understanding, transfer of knowledge, and productive development of societies. This also applies to living cells who are organized in <<microsocietiest; that constantly adjust to their environment through a complex network of signaling pathways. The chemical communication which occurs at various levels results in an integrated exchange of information that is essential for coordinated responses.We wish to present a few features of Cell Communication and Signaling: an open access, peer-reviewed journal devoted to the publication of manuscripts covering all aspects of cell communication, with a particular focus on molecular processes that govern intercellular signaling and events that sustain cellular communication, both in normal and pathological conditions.The launching of Cell Communication and Signaling provides us the opportunity to present a brief overview of basic processes underlying cell communication and the signaling processes that take place within and between cells to permit an efficient communication.

Journal Article↗

PubMed2003

A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis.

The CCN (CYR61 [Cystein-rich61]/CTGF [connective tissue growth factor]/NOV [Nephroblastoma overexpressed]) proteins constitute a family of regulatory factors involved in many aspects of cell proliferation and differentiation. An increasing body of evidence indicates that abnormal expression of the CCN proteins is associated to tumourgenesis. The multimodular architecture of the CCN proteins, and the production of truncated isoforms in tumours, raise interesting questions regarding the participation of each individual module to the various biological properties of these proteins. In this article, we review the current data regarding the involvement of CCN proteins in tumourigenesis. We also attempt to provide structural basis for the stimulatory and inhibitory functions of the full length and truncated CCN proteins that are expressed in various tumour tissues.

Journal Article↗

PubMed2003

CCN3 and calcium signaling.

The CCN family of genes consists presently of six members in human (CCN1-6) also known as Cyr61 (Cystein rich 61), CTGF (Connective Tissue Growth Factor), NOV (Nephroblastoma Overexpressed gene), WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins). Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions.In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.

Journal Article↗

PubMed2003

NOV (CCN3) regulation in the growth plate and CCN family member expression in cartilage neoplasia.

Growth plate chondrocytes undergo a coordinated differentiation process resulting in terminal differentiation and new bone formation. Enchondromas are pre-malignant, benign cartilaginous lesions that arise from growth plate chondrocytes that fail to undergo terminal differentiation. NOV (nephroblastoma overexpressed) is a member of the CCN family of proteins, which share a common multi-modular organization. While the role of NOV in chondrocyte development and cartilage neoplasia is not known, other CCN family members play a role in chondrocyte differentiation, or are differentially regulated in cartilage neoplasia. In embryonic murine growth plates, NOV was expressed in pre-hypertrophic and early hypertrophic chondrocytes. PTHrP treatment (which inhibits terminal differentiation) decreased NOV expression in murine femurs maintained in organ culture, and decreased the activity of a NOV reporter construct in vitro. Expression of the CCN family members NOV, CTGF, CYR61, and WISP-1 was examined in 15 chondrosarcomas of various grades and in three enchondromas. Expression of all of the family members was lower in the higher-grade tumours. As identification of the grade of cartilage neoplasia can sometimes be difficult using histology alone, the level of expression of CCN family members could be a useful adjunct in the determination of tumour grade.

Animals↗

PubMed2003

The CCN3 (NOV) cell growth regulator: a new tool for molecular medicine.

The CCN genes encode secreted signaling proteins that participate in fundamental processes including cell adhesion, proliferation and differentiation, embryogenesis, tissue remodeling and patterning. Abnormal expression of CCN proteins is associated with several pathological conditions, including vascular diseases, fibrosis and cancer. Understanding the structural and functional basis for the variety of biological properties attributed to CCN proteins is an important challenge. It will help the understanding of their roles in the control of cellular proliferation, differentiation and death, thereby allowing their use for early diagnosis and therapy. In an attempt to evaluate the relevance of CCN3 as a useful tool in modern biomedical technologies, the biological properties of the CCN proteins and the data that established their potential usefulness will briefly be reviewed.

Animals↗

PubMed2002

The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway.

We demonstrate a novel interaction of the nephroblastoma overexpressed gene (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV associates with the epidermal growth factor-like repeats of Notch1 by the CT (C-terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the downstream transducers of Notch signaling, were activated by NOV. Expressions of NOV and Notch1 were concomitant in the presomitic mesoderm and later in the myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal cell differentiation. In C2/4 myogenic cells, elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation. These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis.

Animals↗

PubMed2002

The expression of ccn3(nov) gene in musculoskeletal tumors.

The CCN3(NOV) protein belongs to the CCN [cysteine-rich CYR61, connective tissue growth factor (CTGF), nephroblastoma overexpressed gene (Nov)] family of growth regulators, sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Although previous studies have revealed an expression of CCN3 protein in several normal tissues, including kidney, nervous system, lung, muscle, and cartilage, less is known about its expression in tumors. In this study, we analyzed the expression of CCN3 in musculoskeletal tumors, using a panel of human cell lines and tissue samples. An association between CCN3 expression and tumor differentiation was observed in rhabdomyosarcoma and cartilage tumors, whereas, in Ewing's sarcoma, the expression of this protein seemed to be associated with a higher risk to develop metastases. CCN3 expression was found in 15 of 45 Ewing's sarcoma tissue samples. In particular, we did not observe any expression of CCN3 in the 15 primary tumors that did not develop metastases. In contrast, 15 of the 30 primary tumors that developed lung and/or bone metachronous metastases showed a high expression of the protein (P < 0.001, Fisher's test). Our studies indicate that CCN3 is generally expressed in the cells of the musculoskeletal system. This protein may play a role both in normal and pathological conditions. However, the regulation of CCN3 expression varies in the different neoplasms and depends on the type of cells. Thus, as reported for other CCN genes, the biological properties and regulation of expression of CCN3 are dependent on the cellular context and the nature of the cells in which it is produced. Further studies will help to clarify the biological role of this protein in musculoskeletal neoplasms.

Bone Neoplasms↗