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C Bamberger

Publications and source records attributed to C Bamberger.

10 recordsLinked to original sources
PubMed2006

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases.

CEACAM1, also known as biliary glycoprotein (BGP), CD66a, pp120 and C-CAM1, is a member of the CEA immunoglobulin superfamily. CEACAM1 is a putative tumor suppressor based on diminished expression in some solid neoplasms such as colorectal carcinoma. However, CEACAM1 is overexpressed in some tumors such as non-small cell lung cancer. To clarify the mechanism of action of this cell adhesion molecule, we studied thyroid carcinoma that has a spectrum of morphologies and variable behavior allowing separation of proliferation from invasion and metastasis. CEACAM1 is expressed in thyroid carcinoma cell lines derived from tumors that exhibit aggressive behavior. Introduction of CEACAM1 into endogenously deficient WRO cells resulted in reduced cell cycle progression associated with p21 upregulation and diminished Rb phosphorylation. Forced CEACAM1 expression enhanced cell-matrix adhesion and migration and promoted tumor invasiveness. Conversely, small interfering RNA (siRNA)-mediated downregulation of CEACAM1 expression in MRO cells accelerated cell cycle progression and significantly enhanced tumor size in xenografted mice. CEACAM1 is not appreciably expressed in normal thyroid tissue or benign thyroid tumors. In a human thyroid tissue array, CEACAM1 reactivity was associated with metastatic spread but not with increased tumor size. These findings identify CEACAM1 as a unique mediator that restricts tumor growth whereas increasing metastatic potential. Our data highlight a complex repertoire of actions providing a putative mechanism underlying the spectrum of biologic behaviors associated with thyroid cancer.

Adenocarcinoma, Follicular↗
PubMed2001

Identification and tissue distribution of novel KET/p63 splice variants.

The human p53 protein family comprises three members - p53, p63 and p73. Whereas only one p53 variant is known multiple isoforms of p63 and p73 have been described. Depending on the isoform p63 influences p53-responsive genes in a p53-like or -distinct manner. We have cloned multiple splice variants of keratinocyte transcription factor (KET), the rat ortholog of human p63. Several tissue specific variations of exon 1 resulting in different amino-terminal ends were identified. Transactivation properties of the splice variants inversely correlated with the length of the N-termini as determined by activation of the p53-responsive p21 promotor. Multiple KET isoforms are colocalized in different rat tissues. The amino-terminal truncated form DeltaNKETalpha is expressed in epithelial tissues, while expression of the most p53-like KET isotype TAKETgamma was detected in skeletal muscle. Expression of a major KET variant appears to be a cell-type specific rather than a differentiation specific phenomenon.

Alternative Splicing↗
PubMed1998

Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16.

KET is a member of the newly discovered family of proteins that is related to the tumor suppressor p53. Here we describe the molecular cloning of a human cDNA of 4846 bp encoding a protein of 680 amino acids. The human KET protein shares 98% identity with the previously characterized rat homolog. The remarkably high degree of conservation lends support to the notion that KET proteins have important basic functions in development and differentiation. Using the GeneBridge 4 radiation hybrid panel, we have mapped KET to human Chromosome (Chr) 3q27. KET is located between the somatostatin gene SST (proximal) and the apolipoprotein D gene APOD (distal) in a region of conserved synteny to mouse Chr 16. This chromosomal region is deleted in early stages of tumorigenesis of mouse islet cell carcinomas and contains the hitherto unidentified Loh2 gene, a putative suppressor of angiogenesis. The murine homolog Ket was mapped in an interspecific backcross panel and falls into this region of loss of heterozygosity. From our mapping data we infer that KET might act as a tumor suppressor and is considered as a candidate for Loh2.

Amino Acid Sequence↗
PubMed1997

A novel protein with strong homology to the tumor suppressor p53.

The p53 tumor suppressor orchestrates a number of important genes involved in cell-cycle control and apoptosis. Mice deficient for p53 show a high incidence of cancer but are developmentally normal suggesting that compensatory mechanisms exist in embryogenesis and differentiation. The new KET protein is the first mammalian protein with strong homology to p53 in all evolutionary conserved regions. This conservation makes a functional redundancy of the two proteins in cell-cycle control possible. KET is expressed during embryonic development and in certain adult tissues. Among all of the known p53 proteins of different species KET is most closely related to that found in squid. The relationship between KET and the invertebrate p53 protein sheds light on the evolutionary origin of p53. KET appears to be an ancestral p53-related protein in vertebrates with a possible role in development and differentiation while the ubiquitously expressed p53 protein attained its general role as 'guardian of the genome' during evolution.

Amino Acid Sequence↗
PubMed1996

The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): tissue levels, mechanism of action, and potential physiologic role.

BACKGROUND: Alternative splicing of the transcripts of the human glucocorticoid receptor gene results in two mutually exclusive products, the classic, ligand-binding glucocorticoid receptor (hGR alpha), and a dominant negative non-ligand-binding isoform, hGR beta. MATERIALS AND METHODS: We examined the existence of and quantified both hGR alpha and hGR beta isoforms in a panel of human tissues, as well as in intact and fractionated HeLa cells, using specific quantitative Western blots and/or immunocytochemistry. We studied the potential interactions of hGR beta with heat shock protein (hsp) 90 and/or hGR alpha using cross-immunoadsorption/precipitation procedures followed by Western blots. RESULTS: For the first time, we demonstrated the natural existence of the hGR beta protein, which was widely expressed in human tissues. The ratio of immunoreactive hGR alpha to hGR beta varied from 0.2 to 1.0 among different tissues, and was approximately 0.2 in HeLa cells. In the latter, both isoforms were distributed in the cytoplasm and nucleus in the absence of the hormonal ligand, and translocated into the nucleus after addition of dexamethasone. The cytosolic and nuclear hGR alpha-to-hGR beta ratio remained the same before and after dexamethasone exposure, suggesting that upon activation the two isoforms translocated into the nucleus in equal proportions. hGR alpha- and hGR beta-specific antibodies cross-adsorbed and precipitated cytosolic and nuclear glucocorticoid hGR alpha and hGR beta, respectively, as well as hsp90, suggesting that hGR alpha and hGR beta are in complex with hsp90 and/or each other. CONCLUSIONS: The hGR beta protein is widely expressed throughout the human body and present mostly in the cytoplasm of human cells, in complex with hsp90 and other proteins. In the presence of glucocorticoid, hGR beta probably heterodimerizes with ligand-bound hGR alpha and translocates into the nucleus to act as a dominant negative inhibitor of the classic receptor.

Alternative Splicing↗
PubMed1995

Regeneration in the optic nerve of adult rats: influences of cultured astrocytes and optic nerve grafts of different ontogenetic stages.

We have studied the effects of transplanted optic nerves of different ontogenetic stages (E19 to adult), and cultured astrocytes from P2 cerebral cortex on the regeneration of axons in the optic nerve of adult rats. Regeneration was visualized by anterograde tracing with rhodamine-iso-thiocyanate. Grafts were identified with Nuclear Yellow. Astroglia within both the cut optic nerve and the transplants were detected by anti-glial fibrillary acidic protein staining. In control animals (cut optic nerve, 2-3 mm behind the optic disc), only a few neurites were found 15 days after the operation which grew randomly for short distances into the surrounding meningeal sheaths. Perinatal (E19 to P2) optic nerves induced a massive outgrowth of RITC-filled axons from the host optic nerve. The regenerating fibres grew for up to 3 mm towards the graft, ahead of glial fibrillary acidic protein-positive astroglia emanating from the host optic nerve that seemed to follow them. Although the regenerating fibres reached the grafts, they did not penetrate them. Optic nerve grafts of increasing age elicited smaller growth responses; e.g. grafts from P8 promoted only a very limited (several 100 microns) growth response, grafts from P12 and later induced outgrowth comparable with that of control animals. Grafted astrocytes from P2 donors that had previously been grown in culture, were also capable of promoting outgrowth of rhodamine-iso-thiocyanate-filled axons from the host optic nerve. These findings suggest that only astrocytes at an immature stage of differentiation are capable of inducing axon growth from the adult optic nerve. Furthermore, the absence of an obvious cellular bridge between host and graft suggests that the graft effect is probably mediated by the release of astroglia-derived diffusible neurite growth promoting factors.

Animals↗