title: Cytosolic phospholipase A2 alpha regulates cell growth in RET/PTC-transformed thyroid cells.
abstract: Modulation of cytosolic phospholipase A(2) (PLA(2)) expression levels and production of its metabolites have been reported in several tumor types, indicating involvement of arachidonic acid and its derivatives in tumorigenesis. Following our demonstration that the PLA(2) group IV isoform alpha (PLA(2)IV alpha) controls TSH-independent growth of normal thyroid (PCCl(3)) cells, we have investigated the mitogenic role of PLA(2)IV alpha in rat thyroid cells transformed by the RET/PTC oncogenes (PC-PTC cells). We now report that PLA(2)IV alpha acts downstream of the RET/PTC oncogenes in a novel pathway controlling RET-dependent cell proliferation. In addition, we show that PLA(2)IV alpha is in its phosphorylated/active form not only in RET/PTC-transformed cells and in cells derived from human papillary carcinomas but also in lysates from tumor tissues, thus relating constitutive activation of PLA(2)IV alpha to RET/PTC-dependent tumorigenesis. Moreover, p38 stress-activated protein kinase is the downstream effector of RET/PTC that is responsible for PLA(2)IV alpha phosphorylation and activity. In summary, our data elucidate a novel mechanism in the control of thyroid tumor cell growth that is induced by the RET/PTC oncogenes and which is distinguishable from that of other oncogenes, such as BRAF. This mechanism is mediated by PLA(2)IV alpha and should be amenable to targeted pharmacologic intervention.
authors: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy. mariggio@negrisud.it
authors: Stefania
authors: S
authors: Mariggiò
authors: Beatrice Maria
authors: BM
authors: Filippi
authors: Cristiano
authors: C
authors: Iurisci
authors: Luana Katia
authors: LK
authors: Dragani
authors: Valentina
authors: V
authors: De Falco
authors: Massimo
authors: M
authors: Santoro
authors: Daniela
authors: D
authors: Corda
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003600:Cytosol / Q000201:enzymology; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000473:pathology*
chemical_list: D054513:Group IV Phospholipases A2; D013936:Thymidine