Extracellular matrix regulates alpha s1-casein gene expression in rabbit primary mammary cells and CCAAT enhancer binding protein (C/EBP) binding activity

2001 ◽  
Vol 82 (3) ◽  
pp. 371-386 ◽  
Author(s):  
Genevi�ve Jolivet ◽  
Chantal Meusnier ◽  
Gilles Chaumaz ◽  
Louis-Marie Houdebine
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Protein C ◽  
Binding Protein ◽  
Binding Activity ◽  
Mammary Cells ◽  
Casein Gene ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

Growth-dependent inhibition of CCAAT enhancer-binding protein (C/EBP alpha) gene expression during hepatocyte proliferation in the regenerating liver and in culture

1992 ◽  
Vol 12 (6) ◽  
pp. 2553-2560
Author(s):  
D Mischoulon ◽  
B Rana ◽  
N L Bucher ◽  
S R Farmer
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Protein C ◽  
Binding Protein ◽  
Regenerating Liver ◽  
Differentiated Cells ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Alpha Gene ◽  
Rat Tail

As an approach to understanding physiological mechanisms that control the proliferation of highly differentiated cells, we are addressing whether certain hepatic transcription factors participate in mechanisms that control the growth of hepatocytes. We have focused on CCAAT enhancer-binding protein (C/EBP alpha), a transcription factor which is highly abundant in normal liver and is considered to regulate expression of many genes, including some involved in energy metabolism (S. L. McKnight, M. D. Lane, and S. Gluecksohn-Walsh. Genes Dev. 3:2021-2024, 1989). Using Northern (RNA) blot analysis, we have examined the expression of C/EBP alpha mRNA during liver regeneration and in primary cultures of hepatocytes. C/EBP alpha mRNA levels decrease 60 to 80% within 1 to 3 h after partial hepatectomy as the cells move from G0 to G1 and decrease further when cells progress into S phase. Run-on transcription analysis is in agreement with the Northern blot data, thus suggesting that C/EBP alpha is transcriptionally regulated in regenerating liver. C/EBP alpha mRNA expression also decreases dramatically during the growth of freshly isolated normal hepatocytes cultured under conventional conditions (on dried rat tail collagen; stimulated to proliferate by epidermal growth factor [EGF] and insulin). Cultures of hepatocytes on rat tail collagen in the presence or absence of EGF clearly show that within 3 h, EGF depresses C/EBP alpha mRNA expression and that this effect is substantially greater by 4 h. Inhibition of protein synthesis in the liver by cycloheximide or in cultured hepatocytes by puromycin or cycloheximide effectively blocks the down-regulation of C/EBP alpha gene expression, apparently by stabilizing the normal rapid turnover of the C/EBP alpha mRNA (half-life of <2 h). This drop in C/EBP alpha gene expression in response to activation of hepatocyte growth is consistent with the proposal that C/EBP alpha has an antiproliferative role to play in highly differentiated cells (R. M. Umek, A. D. Friedman, and S. L. McKnight, Science 251: 288-292, 1991).

scholarly journals Growth-dependent inhibition of CCAAT enhancer-binding protein (C/EBP alpha) gene expression during hepatocyte proliferation in the regenerating liver and in culture.

1992 ◽  
Vol 12 (6) ◽  
pp. 2553-2560 ◽  
Author(s):  
D Mischoulon ◽  
B Rana ◽  
N L Bucher ◽  
S R Farmer
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Protein C ◽  
Binding Protein ◽  
Regenerating Liver ◽  
Differentiated Cells ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Alpha Gene ◽  
Rat Tail

As an approach to understanding physiological mechanisms that control the proliferation of highly differentiated cells, we are addressing whether certain hepatic transcription factors participate in mechanisms that control the growth of hepatocytes. We have focused on CCAAT enhancer-binding protein (C/EBP alpha), a transcription factor which is highly abundant in normal liver and is considered to regulate expression of many genes, including some involved in energy metabolism (S. L. McKnight, M. D. Lane, and S. Gluecksohn-Walsh. Genes Dev. 3:2021-2024, 1989). Using Northern (RNA) blot analysis, we have examined the expression of C/EBP alpha mRNA during liver regeneration and in primary cultures of hepatocytes. C/EBP alpha mRNA levels decrease 60 to 80% within 1 to 3 h after partial hepatectomy as the cells move from G0 to G1 and decrease further when cells progress into S phase. Run-on transcription analysis is in agreement with the Northern blot data, thus suggesting that C/EBP alpha is transcriptionally regulated in regenerating liver. C/EBP alpha mRNA expression also decreases dramatically during the growth of freshly isolated normal hepatocytes cultured under conventional conditions (on dried rat tail collagen; stimulated to proliferate by epidermal growth factor [EGF] and insulin). Cultures of hepatocytes on rat tail collagen in the presence or absence of EGF clearly show that within 3 h, EGF depresses C/EBP alpha mRNA expression and that this effect is substantially greater by 4 h. Inhibition of protein synthesis in the liver by cycloheximide or in cultured hepatocytes by puromycin or cycloheximide effectively blocks the down-regulation of C/EBP alpha gene expression, apparently by stabilizing the normal rapid turnover of the C/EBP alpha mRNA (half-life of <2 h). This drop in C/EBP alpha gene expression in response to activation of hepatocyte growth is consistent with the proposal that C/EBP alpha has an antiproliferative role to play in highly differentiated cells (R. M. Umek, A. D. Friedman, and S. L. McKnight, Science 251: 288-292, 1991).

DDRE-30. CELL-PENETRATING PEPTIDE ANTAGONIST OF CCAAT/ENHANCER BINDING PROTEIN ß DISPLAYS POTENT ANTI-GLIOBLASTOMA ACTIVITY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi80-vi81
Author(s):  
Jim Rotolo ◽  
Lila Ghamsari ◽  
Ricardo Ramierez ◽  
Mark Koester ◽  
Siok Leong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Subcutaneous Xenograft ◽  
Peptide Antagonist ◽  
Anti Tumor Activity

Abstract CCAAT/Enhancer Binding Protein Beta (C/EBPß) is a transcription factor overexpressed in glioblastoma (GBM). Mechanistically, C/EBPß is a master regulator of mesenchymal transition in GBM, and its increased expression correlates with mesenchymal differentiation and predicts poor clinical outcome. C/EBPß activity requires dimerization with co-factors such as CREB/ATF family members via leucine zipper interactions. ST101 is a novel peptide antagonist of C/EBPß currently being evaluated in a Phase 1/2 clinical study in patients with advanced unresectable and metastatic solid tumors. ST101 binds to the C/EBPß leucine zipper, thereby preventing dimer formation and inhibiting its transcriptional activity, resulting in selective tumor cell cytotoxicity. Here, we describe ST101 non-clinical anti-tumor activity against GBM. In vitro studies in T98G and U251 cells demonstrate ST101 dose-dependent impact of cell viability (EC50 of 2.2 and 1.2 μM, respectively), accompanied by significant impact on C/EBPß-mediated gene expression as determined by qPCR analysis. In contrast, normal human mononuclear and epithelial cells were not sensitive to ST101 (EC50 &gt; 80 μM). In vivo, ST101 displayed significant anti-tumor activity in a U251 GBM subcutaneous xenograft model, resulting in 81.4% tumor growth inhibition (TGI) vs. control and undetectable tumors in 50% of animals. Following ST101 exposure tumors displayed reduced BIRC3 and ID2 gene expression, and significantly increased cleaved caspase 3 immunostaining indicative of cell death induction. In U251 tumors, subtherapeutic ST101 (&lt; 5% TGI) in combination with temozolomide (&lt; 5% TGI) resulted in 52.8% TGI, significantly greater than either single-agent alone. Similarly, in a temozolomide-refractory T98G GBM subcutaneous xenograft model, ST101 (41.6% TGI) in combination with TMZ (&lt; 5% TGI) resulted in significant anti-GBM response (72.4% TGI). These data emphasize the potential of ST101 as a potent peptide therapeutic for GBM.

scholarly journals Gene Expression of CCAAT/Enhancer-Binding Protein .DELTA. Mediated by Autoregulation Is Repressed by Related Gene Family Proteins.

2000 ◽  
Vol 23 (12) ◽  
pp. 1424-1429 ◽  
Author(s):  
Atsuhiro TANABE ◽  
Chizumi KUMAHARA ◽  
Shigehiro OSADA ◽  
Tsutomu NISHIHARA ◽  
Masayoshi IMAGAWA
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Binding Protein ◽  
Related Gene ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

CCAAT/enhancer binding protein δ regulates glial proinflammatory gene expression

2013 ◽  
Vol 34 (9) ◽  
pp. 2110-2124 ◽  
Author(s):  
Tony Valente ◽  
Marco Straccia ◽  
Nuria Gresa-Arribas ◽  
Guido Dentesano ◽  
Josep M. Tusell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Proinflammatory Gene ◽  
Proinflammatory Gene Expression
Sign in / Sign up

Export Citation Format

Share Document