SPHINGOSINE KINASE-1 EXPRESSION IN HUMAN TUMORS.

FIORE LUCIANO; LANG CECILIA; FERMENTO M EUGENIA; GANDINI NORBERTO ARIEL; MATURI HORACIO; STERIN-SPEZIALE NORMA B; CURINO ALEJANDRO C; FACCHINETTI MARIA M

Mar del Plata

Congreso; 43 Congreso Anual de la Sociedad Argentina de Investigación en Bioquimica y Biologia Molecular; 2007

Sociedad Argentina de Investigacion en Bioquimica y Biologia Molecular

Sphingosine kinase-1 (SK1) is a key enzyme that regulates the balance between cellular levels of the pro-apoptotic molecules sphingosine (SPH) and ceramide (CER) and the growth-promoting lipid sphingosine-1-phosphate (S1P). SK1 has been shown to be upregulated in lung cancer and in glioblastoma and to confer resistance to chemotherapy in some cell types. However, few studies have been performed showing expression in human tumors. Therefore, we focused on studying the role that this protein plays in human tumor progression by analyzing its expression in breast and colon adenocarcinomas, gliomas, head and neck squamous cell carcinomas (HNSCC) and clear cell renal carcinomas (CCRC). We first performed a screening of SK1 expression in HNSCC samples by using the recently developed tissue array: we observed that the enzyme was expressed in 85.7% of tumors (162 out of 189). To obtain more qualitative information we studied different tumor tissues by regular immunohistochemistry and observed that the staining was stronger in tumor cells when compared with adjacent tissue and that it had a cytoplasmic localization. We also studied protein expression on a mouse model of breast cancer (MMTV-PyMT). The results shown confirmed that SK1 may play a role in human tumor progression.