title: LY294002 induces in vitro apoptosis and overexpression of p75NTR in human uterine leiomyosarcoma HTB 114 cells.
abstract: Uterine leiomyosarcoma is a severe neoplasia resistant to conventional therapies. In previous studies, we have shown that human SK-UT-1 (ATCC HTB114) uterine leiomyosarcoma cell line secretes nerve growth factor (NGF) and expresses its receptors tyrosine kinase A receptor (TrKA) and low affinity nerve growth factor receptor (p75NTR). Furthermore, we have demonstrated that direct chemical inhibition or IgG neutralization of TrKA receptor induce apoptosis through p75NTR. In the present study, HTB114 cells were exposed to the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 with and without β-NGF: apoptosis, cell cycle, activation of caspase-3 and protein kinase B (AKT) and TrKA/p75NTR phenotypic expression were evaluated. According to the type of exposure, LY294002 not only induced a relevant increase in apoptosis, but also produced a novel and unexpected phenotypic modulation of the NGF receptors with a downregulation of TrKA and an upregulation of p75NTR. This latter increase enhanced HTB114 apoptosis. Our study confirms that the interference on NGF transduction is a promising therapeutical approach in uterine leiomyosarcoma.
authors.affiliation: a Department of Surgery and Biomedical Sciences , Section of Human Anatomy, Clinical and Forensic, School of Medicine , Perugia , Italy and.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pistilli
authors.affiliation: a Department of Surgery and Biomedical Sciences , Section of Human Anatomy, Clinical and Forensic, School of Medicine , Perugia , Italy and.
authors.forename: Mario
authors.initials: M
authors.lastname: Rende
authors.affiliation: a Department of Surgery and Biomedical Sciences , Section of Human Anatomy, Clinical and Forensic, School of Medicine , Perugia , Italy and.
authors.forename: Lucia
authors.initials: L
authors.lastname: Crispoltoni
authors.affiliation: b Biology and Degenerative Medicine Division, The Nicola Cerulli Institute of Translational Research for the Musculoskeletal System - LPMRI , Arezzo , Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Montagnoli
authors.affiliation: a Department of Surgery and Biomedical Sciences , Section of Human Anatomy, Clinical and Forensic, School of Medicine , Perugia , Italy and.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Stabile
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma / Q000473:pathology*; D009025:Morpholines / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D020917:Receptor, trkA / Q000096:biosynthesis; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D014594:Uterine Neoplasms / Q000473:pathology*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C502240:NGF protein, human; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017475:Receptors, Nerve Growth Factor; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: HTB114; LY294002; PI3K; nerve growth factor; p75NTR; tyrosine kinase A receptor