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 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.
Calonghi
Natalia
N
Department of Biochemistry G. Moruzzi, Alma Mater Studiorum, University of Bologna, Italy. natalia.calonghi@unibo.it
Pagnotta
Eleonora
E
Parolin
Carola
C
Tognoli
Cristina
C
Boga
Carla
C
Masotti
Lanfranco
L
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019073:HT29 Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D013229:Stearic Acids / Q000494:pharmacology*
D013229:Stearic Acids; D019938:Cyclin D1; C070375:9-hydroxystearic acid; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases