Oncogene-induced cellular senescence: causal factor in the growth arrest of pituitary microadenomas?

Pituitary microadenomas are exceedingly common in the general population, and only a very few progress to a size of more than a few millimetres. The early and total, or near- total, growth arrest preventing the outgrowth of these adenomas calls to mind the phenomenon of oncogene- induced cellular senescence (OIS), a growth arrest response brought about by oncogenic signalling. In the past, OIS has been demonstrated in a variety of benign neoplastic lesions, in animal models as well as in man. OIS results from the activation of powerful antiproliferative signalling networks, and presumably acts as a protective response preventing the outgrowth of early neoplastic lesions that are driven by a single or a very few oncogenic lesions. A few recent studies on pituitary tumorigenesis in Rb+/- mice, as well as some preliminary observations in human pituitary adenomas, lend support to the idea that OIS is also an important mediator of growth arrest in these occult pituitary tumours. If so, the fact that over 99.9% of pituitary adenomas never produce clinical problems of mass effect attests to the efficacy of this response.