scholarly journals Genetic Screens for Enhancers of brahma Reveal Functional Interactions Between the BRM Chromatin-Remodeling Complex and the Delta-Notch Signal Transduction Pathway in Drosophila

Genetics ◽  
2005 ◽  
Vol 170 (4) ◽  
pp. 1761-1774 ◽  
Author(s):  
Jennifer A. Armstrong ◽  
Adam S. Sperling ◽  
Renate Deuring ◽  
Laurina Manning ◽  
Sarah L. Moseley ◽  
...  
2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14501-14501
Author(s):  
H. Zhang ◽  
Y. Ye ◽  
F. Xu ◽  
J. Zhou ◽  
S. Wang

14501 Background: As is known the polycomb group protein BMI1 has been shown to support normal stem cell proliferation via its putative stem cell factor function. However, the potential molecular mechanism of BMI1 act as a cancer stem cell factor may also promote cancer development is unclear. In this study we demonstrated for the first time that Notch signal transduction pathway regulating expression of Bmi1 in colorecta caner cells and investigate the Notch1 mRNA and Bmi1 mRNA level in human colorectal cancer samples and their correlation with clinicopathological parameters of colorectal cancer. Methods and Results: We assessed Notch1 and Bmi1 mRNA in 50 cases of colorectal cancer and adjacent normal tissue by RT-PCR. The immunohistochemistry was used to determine the expression of ICN and in the 50 tissues of colorectal cancer and normal mucosa. Bmi1 SW480 cells were treated with DAPT (g-secretase inhibitor) at different times. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of ICN, Bmi1 were measured by western blot. Notch1 and Bmi1 mRNA level were increased in colorectal cancer compared with adjacent normal mucosa (P<0.05), the median values were 1.97-fold, 1.88-fold, respectively. It was found that overexpression of Notch1 and Bmi1 was related to differentiation and lymph nodes metastasis in colorectal cancer (P<0.05). The correlation between Notch1 and Bmi1 mRNA level, ICN and Bmi1 protein level are significant at the 0.01 level. Treating SW480 with DAPT, resulted in significant growth inhibition, apoptosis induction and downregulation of ICN and Bmi1. Conclusion: Our results show that overexpression of Notch1 and Bmi1 may play a critical role in the development of colorectal cancer. Notch1 signal transduction pathway regulating expression of Bmi1 in colorectal cancer cells.Blockade of Notch1 signal pathway can inhibit proliferation and accelerate apoptosis of colorectal cancer. [Key words] Colorectal cancer; BMI1; Signal transducers and activators of transcription3; Western blotting No significant financial relationships to disclose.


2020 ◽  
Vol 8 (17) ◽  
pp. 1057-1057
Author(s):  
Shuguang Ren ◽  
Xiangmei Zhang ◽  
Yueyang Hu ◽  
Jianhua Wu ◽  
Yingchao Ju ◽  
...  

1998 ◽  
Vol 12 (15) ◽  
pp. 2269-2277 ◽  
Author(s):  
H.-Y. Kao ◽  
P. Ordentlich ◽  
N. Koyano-Nakagawa ◽  
Z. Tang ◽  
M. Downes ◽  
...  

2005 ◽  
Vol 83 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Katherine L Dunn ◽  
Paula S Espino ◽  
Bojan Drobic ◽  
Shihua He ◽  
James R Davie

Stimulation of the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway results in a multitude of events including expression of the immediate-early genes, c-fos and c-myc. Downstream targets of this stimulated pathway are the mitogen- and stress-activated protein kinases (MSK) 1 and 2, which are histone H3 kinases. In chromatin immunoprecipitation assays, it has been shown that the mitogen-induced phosphorylated H3 is associated with the immediate-early genes and that MSK1/2 activity and H3 phosphorylation have roles in chromatin remodeling and transcription of these genes. In oncogene-transformed fibroblasts in which the Ras-MAPK pathway is constitutively active, histone H1 and H3 phosphorylation is increased and the chromatin of these cells has a more relaxed structure than the parental cells. In this review we explore the deregulation of the Ras-MAPK pathway in cancer, with an emphasis on breast cancer. We discuss the features of MSK1 and 2 and the impact of a constitutively activated Ras-MAPK pathway on chromatin remodeling and gene expression.Key words: Ras, mitogen-activated protein kinase signal transduction pathway, histone H3 phosphorylation, MSK1, breast cancer.


Development ◽  
1993 ◽  
Vol 119 (Supplement) ◽  
pp. 41-46 ◽  
Author(s):  
E. Hafen ◽  
B. Dickson ◽  
T. Raabe ◽  
D. Brunner ◽  
N. Oellers ◽  
...  

The specification of the R7 photoreceptor cell fate in the developing eye of Drosophila depends on the local activation of the sevenless (sev) receptor tyrosine kinase (RTK) by boss, a protein expressed on the membrane of the neighboring R8 cell. Constitutive activation of the scv receptor results in a dosage dependent increase in the number of R7 cells per ommatidium. Genetic screens have been used to identify mutations that alter the efficiency of signal transduction. Subsequent molecular characterization of the corresponding genes has led to the identification of a number of proteins involved in transducing the signal from the receptor to the nucleus. In contrast to the receptor and its ligand, these components are shared between different signal transduction pathways not only in Drosophila but homologous components are also involved in signal transduction in other organisms.


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