Benign tumors from the human nervous system express high levels of survivin and are resistant to spontaneous and radiation-induced apoptosis

Abstract

Survivin, an inhibitor of apoptosis, is over-expressed in foetal tissues and human cancers, but it is almost undetectable in normal tissues. Here we have assessed the level of the survivin protein in some benign tumors of the nervous system: meningioma, schwannoma, low-grade ependymoma, pilocytic astrocytoma and pituitary adenoma. Using immuno-blot analysis we present evidence that these low-grade tumors are positive for survivin expression. In agreement, flow cytometrical analysis showed that both spontaneous and radiation-induced apoptosis levels are very low in these neoplasms. Using host cell reactivation assay we have also shown that these tumor cells are proficient in the repair of γ-ray-induced DNA damage. However, they are deficient in the removal of ultraviolet (UV) light-induced DNA photolesions, especially the shwannoma- and the pituitary adenoma-derived cells. These results suggest that survivin overexpression may be an early event in the stepwise tumoregenesis and hence could be responsible for the onset as well as the growth advantage during tumoregenic progression of malignant as well as benign neoplasms.