Regulation of PTEN expression in neuronal apoptosis

PTEN phosphatase is a tumor suppressor gene that dephosphorylates phosphati dylinositol phosphates. PTEN restrains the function of a major antiapoptoti c and survival pathway involving phosphoinositide 3-kinase and Akt kinase. Our purpose was to find out whether apoptotic inducers affect the expressio n of PTEN in cerebellar granule neurons and neuroblastoma 2a cells (Neuro-2 a). PTEN mRNA expression showed a major 5.5-kb and a lower abundance 2.5-kb transcripts. In Neuro-2a cells, serum withdrawal induced a prominent, cont inuous decrease both in 5.5- and 2.5-kb transcripts of PEN mRNA. Simultaneo usly, the expression level of 56-kDa PTEN protein decreased in Neuro-2a cel ls. The decrease in PTEN expression precedes apoptotic changes observed aft er serum withdrawal. On the contrary, okadaic acid and etoposide only sligh tly affected the expression of PTEN although they induce a prominent apopto sis in Neuro-2a cells. In cerebellar granule neurons, okadaic acid treatmen t induced a prominent increase in PTEN mRNA expression after 6-h treatment, both at the 5.5- and 2.5-kb transcripts. The early response in PTEN mRNA e xpression disappeared in 5.5-kb transcripts already at 12 h and in the case of 2.5-kb transcripts it lasted up to 24 h. Potassium deprivation, known t o induce apoptosis in cerebellar granule cells, did not affect PTEN mRNA ex pression but together with serum deprivation induced a clear decrease in th e 5.5-kb PTEN transcripts. It seems that the changes in PTEN expression lev el and neuronal apoptosis are not related to each other in general but the expression of PTEN phosphatase seems to regulate certain apoptotic signals affecting phosphoinositide 3-kinase function. (C) 1999 Elsevier Science B.V . All rights reserved.