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J Cortner

Publications and source records attributed to J Cortner.

9 recordsLinked to original sources
PubMed1995

The Met-HGF/SF autocrine signaling mechanism is involved in sarcomagenesis.

Hepatocyte growth factor/scatter factor (HGF/SF) can elicit a wide variety of effects upon cells expressing its receptor, the tyrosine kinase proto-oncogene product Met, including mitogenicity, motility, and morphogenesis. Normally, met expression is restricted to epithelial cells and is activated in a paracrine fashion by HGF/SF secreted from cells of mesenchymal origin. In this chapter, we review data showing that: (i) met over-expression in HGF/SF-expressing NIH/3T3 fibroblasts leads to sarcomagenesis and metastasis via an autocrine mechanism; (ii) Met-HGF/SF autocrine signalling occurs to a low level in normal fibroblasts and to a much greater extent in human sarcomas and sarcoma cell lines; (iii) met expression is enhanced as p53-deficient fibroblasts are passaged in vitro and (iv) met and HGF/SF over-expression are selected for during tumorigenesis of p53-deficient late-passage fibroblasts. Thus, loss of p53 predisposes a mesenchymal cell to over-express met and high level Met-HGF/SF autocrine signaling in mesenchymal cells promotes both sarcomagenesis and metastasis through inappropriate induction of the pleiotropic responses to Met-HGF/SF stimulation.

3T3 Cells↗
PubMed1993

An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes.

The proto-oncogene Raf-1 is a cytoplasmic serine/threonine kinase implicated in the signaling process in cell proliferation. To determine if Raf-1 is sufficient and necessary to transmit mitogenic signals to growth-responsive genes, we examined the effect of constitutively activated (v-raf) or inhibitory (Raf-C4) Raf-1 proteins on reporter gene activation in transient expression assays of NIH 3T3 cells. In serum-starved cells, v-raf strongly activated transcription from the promoters of the immediate-early genes c-fos and egr-2, as well as the proximal or B promoter of the late growth response gene rep-3 (rep-3b). Two other late response gene promoters, cad and dhfr, were only modestly activated by v-raf, however. An individual serum response element from the c-fos or egr-2 promoter conferred both serum-inducibility and v-raf-responsiveness to a heterologous promoter. Consistent with the degree to which antisense c-raf-1 RNA and dominant-negative Raf-1 proteins interfere with NIH 3T3 cell proliferation, Raf-C4 reduced serum-induced transcription from the egr-2 and rep-3b promoters in a dose-dependent manner by 50%. In contrast, Raf-C4 did not significantly reduce transcription from the c-fos or cad promoters or the serum response element-driven heterologous promoters. We conclude that Raf-1 is both sufficient and necessary to activate a subset of early and late growth response genes.

3T3 Cells↗
PubMed1992

krox 20 messenger RNA and protein expression in the adult central nervous system.

krox 20 is an inducible immediate early response gene. To determine if krox 20 has a physiological role in the adult central nervous system (CNS), this study sought to demonstrate the presence of krox 20 in adult rat brain. RNA analysis showed the presence of krox 20 transcripts in the CNS, including the cortex. Polyclonal antibodies to a Krox 20 fusion protein demonstrated 79 and 55 kDa antigens in nuclear CNS homogenates. Neither RNA nor protein analysis was able to demonstrate an induction of krox 20 by a seizure at times when other immediate early response genes are known to be induced. Immunohistochemical analysis revealed staining at several levels throughout the nervous system. This staining was predominantly nuclear, consistent with the role of krox 20 as a transcription factor. These data show that krox 20 is present in the adult CNS, yet differs in response to stimuli as compared to other related transcription factors with a zinc finger motif, such as NGFI-A and NGFI-C.

Animals↗
PubMed1991

Cell cycle analysis of Krox-20, c-fos, and JE expression in proliferating NIH3T3 fibroblasts.

We have shown that early growth response genes which were identified on the basis of their expression during the G0 to G1 transition can also be induced in proliferating fibroblasts. The expression of Krox-20 and c-fos mRNAs increased dramatically upon stimulation of cell populations of increasing density and correlated with the percentage of cells in the G0-G1 stages of the cell cycle. However, fractionation of serum-stimulated cultures into cell cycle stage-specific subpopulations using fluorescence-activated cell sorting revealed that the levels of Krox-20 and c-fos mRNAs were equal in all stages of the cell cycle. This result was corroborated by serum and cycloheximide stimulation of stage-specific fractions separated by centrifugal elutriation. Expression of the immediate-early gene JE was also induced in all stages of the cell cycle in the elutriated fractions. Thus, although the amount of induced Krox-20, c-fos, and JE mRNA correlated with the number of quiescent cells in a proliferating population, expression of all three genes occurred to the same extent in all stages of the cell cycle at a given culture density. Possible explanations for the density-associated increase in induced expression are discussed. We have demonstrated that there are both transcriptional and posttranscriptional components to the stimulated expression of the Krox-20 and c-fos genes in proliferating fibroblasts. Since the increased expression of these genes has the same steady-state and transcription rate kinetics as serum response factor-mediated induction, we are currently investigating the role of serum response factor in serum-induced expression in proliferating cells.

3T3 Cells↗
PubMed1990

Identification of the serum-responsive transcription initiation site of the zinc finger gene Krox-20.

The Krox-20 gene is rapidly and transiently induced when quiescent 3T3 cells are stimulated to reenter the proliferative cycle. We identified the major serum-responsive transcription initiation site and found that it differs from the initiation sites previously identified for the Krox-20 gene. Transcripts from the major serum-responsive initiation site increased at least 40-fold in serum-stimulated cells compared with logarithmically growing cells.

Animals↗