P27, SKP2, and extra-cellular signal-related kinase signalling in human salivary gland mucoepidermoid carcinoma.
Extra-cellular signal-related kinase (ERK) can modulate P27 in several ways. ERK is phosphorylated in a subset of salivary gland mucoepidermoid carcinoma (MEC). We determined immunohistochemical expression of P27, SKP2, cyclin A, Ki67, phospho-RB, and phospho-ERK in 43 MEC. SKP2 correlated with tumour size, microscopic grade, and a worse prognosis. Cyclin A and Ki67 also predicted prognosis, and were correlated with SKP2. P27 did not predict prognosis. P27 had no inverse relationship with SKP2, and correlated with neither Ki67 nor cyclin A. Instead, P27 high expressers had higher levels of phospho-ERK and phospho-RB. When highly expressed, P27 co-localized with cyclin D1 in the nuclei. Relationships of P27 with ERK and RB and its nuclear co-localization with cyclin D1 favour the hypothesis that P27 is in complexes with cyclin D1. This may explain why P27 in contrast to SKP2 and cyclin A does not correlate with tumour cell proliferation and prognosis.
Handra-Luca
Adriana
A
Service d'Anatomie Pathologique, AP-HP Hôpital Jean Verdier and Université Paris 13/Nord, France.
Ruhin
Blandine
B
Lesty
Claude
C
Fouret
Pierre
P
D014408:Biomarkers, Tumor / Q000378:metabolism*; D018277:Carcinoma, Mucoepidermoid / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D056741:Cyclin D; D016213:Cyclins / Q000378:metabolism; D018572:Disease-Free Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D056741:Cyclin D; D016213:Cyclins; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen; D048049:Extracellular Signal-Regulated MAP Kinases