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

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [1];  [1];  [1];  [2];  [1]
  1. Department of Biochemistry 'G. Moruzzi', Alma Mater Studiorum, University of Bologna (Italy)
  2. Department of Organic Chemistry 'A. Mangini', Alma Mater Studiorum, University of Bologna (Italy)
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.
OSTI ID:
20798882
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 342; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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