Journal
NEUROENDOCRINOLOGY
Volume 84, Issue 4, Pages 217-221Publisher
KARGER
DOI: 10.1159/000097486
Keywords
pituitary adenomas; epigenetics; apoptosis; pituitary tumour apoptosis gene (PTAG)
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Although multiple different cancers have been described, it is likely that these tumour types share a small, and common, number of newly acquired functional capabilities. Tumours that arise within the pituitary gland are no exception with respect to these new functional capabilities. Although compelling evidence for self-sufficiency in growth signals is presented, loss of functional tumour suppressor genes by classic mechanisms has not been clearly established. However, and in this context, methylation-mediated or -associated gene silencing, in particular of tumour suppressor genes, has been reported by numerous investigators in this tumour type. More recently, a search for novel genes on the basis of their inappropriate methylation has led to identification of a novel pro-apoptotic gene. Its pituitary tumour derivation and role in drug-induced apoptosis resulted in the acronym PTAG (pituitary tumour apoptosis gene) being assigned to this gene. In a model pituitary tumour cell line, AtT20, expression of PTAG per se had no discernible effects on proliferation, cell cycle profile or viability. However, enforced expression was associated with a significantly increased sensitivity to the apoptotic effects induced by bromocriptine challenge. Apoptosis was mediated through caspase activation and associated with DNA fragmentation as determined by TUNEL labelling. Similar findings are also evident in the rodent pituitary cell line, GH3 and our data shows that drugs other than bromocriptine, and that engage characterized receptors, elicit a PTAG-augmented apoptotic response. The isolation of novel genes, on the basis of their methylation status, offers a significant advantage with respect to our understanding of tumorigenesis in both the pituitary and other tumour types. The reversal of apparent gene silencing may lead to tumour cell 'sensitisation' to chemo- and radio-therapeutic treatment strategies. Copyright (c) 2006 S. Karger AG, Basel.
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