title: Selective reduction of extracellular signal-regulated protein kinase (ERK) phosphorylation in squamous cell carcinoma of the larynx.
abstract: Mitogen-activated protein kinase (MAPK) cascades transmit and amplify signals involved in cell proliferation as well as in cell death. In this study, the potential derangement of MAPK pathways has been evaluated in human squamous cell carcinomas (SCC) of the larynx. The expression and activity of the MAPK p38, ERK1/2p44/p42 and JNK/SAPKp46/p54 have been investigated by immunoblot analysis of tissue homogenates in 27 samples of primary laryngeal cancer and in 27 paired non-neoplastic laryngeal mucosa. On the same tissues, the activation of MAPK JNK/SAPKp46/p54 was also analyzed by an ELISA assay. The results obtained showed that both total and phosphorylated levels of JNK/SAPKp46/p54 and p38 were not different between tumor and normal samples. Conversely, while total protein levels for both ERK1p44 and ERK2p42 were not statistically different between tumor and normal samples, the analysis of the level of the activated forms of ERK1/2 showed a statistically significant decreased phosphorylation of both isoforms in the tumor samples compared to the control tissues. The rate of reduction was similar for both isoforms. Immunohistochemical analysis of all the activated MAPK (p38, JNK/SAPKp46/p54 and ERK1/2p44/p42) in both laryngeal SCC and normal mucosa demonstrated no difference of cellular localization. Activated ERK1/2p44/p42 and activated p38 demonstrated a nucleo-cytoplasmic distribution whereas activated JNK/SAPKp46/p54 were localized into the cytoplasmic membrane. The decreased activity of ERK1/2p44/42 in laryngeal SCC might reflect alterations in tumor suppressing activity or might derive from the interplay among various transduction pathways.
authors.affiliation: Department of Otorhinolaryngology - Head and Neck Surgery, 20052 Monza (MI), Italy. werner.garavello@unimib.it
authors.forename: Werner
authors.initials: W
authors.lastname: Garavello
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nicolini
authors.forename: Alessia
authors.initials: A
authors.lastname: Aguzzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Maggioni
authors.forename: Biagio Eugenio
authors.initials: BE
authors.lastname: Leone
authors.forename: Paola
authors.initials: P
authors.lastname: Viganò
authors.forename: Renato Maria
authors.initials: RM
authors.lastname: Gaini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tredici
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D007830:Larynx / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048291:Mitogen-Activated Protein Kinase 12 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048291:Mitogen-Activated Protein Kinase 12; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases