9-Hydroxystearic acid interferes with EGF signalling in a human colon adenocarcinoma

The epidermal growth factor has long been known to be strictly correlated with the highly proliferating activities of cancer cells and primary tumors. Moreover, in the nucleus, the epidermal growth factor/epidermal growth factor receptor complex (EGF/EGFR) functions as a transcriptional regulator th...

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Veröffentlicht in:Biochemical and biophysical research communications 2006-04, Vol.342 (2), p.585-588
Hauptverfasser: Calonghi, Natalia, Pagnotta, Eleonora, Parolin, Carola, Tognoli, Cristina, Boga, Carla, Masotti, Lanfranco
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container_issue 2
container_start_page 585
container_title Biochemical and biophysical research communications
container_volume 342
creator Calonghi, Natalia
Pagnotta, Eleonora
Parolin, Carola
Tognoli, Cristina
Boga, Carla
Masotti, Lanfranco
description The epidermal growth factor has long been known to be strictly correlated with the highly proliferating activities of cancer cells and primary tumors. Moreover, in the nucleus, the epidermal growth factor/epidermal growth factor receptor complex (EGF/EGFR) functions as a transcriptional regulator that activates the cyclin D1 gene. 9-hydroxystearic acid (9-HSA) induces cell proliferation arrest and differentiation in HT29 colon cancer cells by inhibiting histone deacetylase 1 (HDAC1). 9-HSA-treated HT29, when stimulated with EGF, are not responsive and surprisingly undergo a further arrest. In order to understand the mechanisms of this effect, we analyzed the degree of internalization of the EGF/EGFR complex and its interactions with HDAC1. It appears that HDAC1, as modified by 9-HSA, is unable to associate with cyclin D1, interfering with the cell proliferation program, and sequesters the EGF/EGFR complex interrupting the transduction of the mitogenic signal.
doi_str_mv 10.1016/j.bbrc.2006.02.008
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subjects 60 APPLIED LIFE SCIENCES
9-HSA
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
ALBUMINS
BLOOD SERUM
CARCINOMAS
CELL NUCLEI
CELL PROLIFERATION
Cell Proliferation - drug effects
Colon cancer cell
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
Cyclin D1
Cyclin D1 - antagonists & inhibitors
Cyclin D1 - biosynthesis
Cyclin D1 - genetics
EGFR
Epidermal Growth Factor - antagonists & inhibitors
Epidermal Growth Factor - pharmacology
Epidermal Growth Factor - physiology
Fluorescent Antibody Technique
GENES
GROWTH FACTORS
HDAC1
Histone Deacetylase 1
Histone Deacetylases - metabolism
HT29 Cells
Humans
LARGE INTESTINE
Receptor, Epidermal Growth Factor - metabolism
RECEPTORS
Signal Transduction - drug effects
Stearic Acids - pharmacology
title 9-Hydroxystearic acid interferes with EGF signalling in a human colon adenocarcinoma
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