Endocrine Abstracts

Neoplastic thyroid diseases (multinodular goiter (MNG), follicular adenoma, differentiated (DTC) and undifferentiated thyroid carcinoma) have a higher incidence in women than in men. In fact, in the last ten years, DTC is the only cancer increasing the frequency in women, with an incidence similar to ovarian carcinoma or lymphomas.

TGFb is a secreted factor important in the normal function of the thyrocyte. It has two independent actions: a fast antiproliferative action, inhibiting cell division through Smads and p15Ink, and an apoptotic action, decreasing p27Kip1 levels and activating Cdk2. In PC2 we have demonstrated that p27Kip1 overexpression blocked TGFb-induced apoptosis and induced a new slow-proliferating action, leading to a slow, but steady cell cycle that increases cell numbers in presence of TGFb.

In this study we have performed microarrays expression study in PC2 cells transiently tranfected with p27Kip1-expressing vectors (or the corresponding empty vector as control), with or without TGFb treatment.

In summary our results show that TGFbeta, apoptotic or anti proliferating genes are increased at the same time that anti-apoptotic genes are decreased in response to TGFb treatment. Interesting, p27Kip1expression reversed this signature causing induction of anti-apoptotic genes and reduction in apoptotic or antiproliferative genes after TGFb treatment. For example, BAX beta is increased in TGFbeta-treated cells but decreased in presence of TGFbeta in p27kip1-overespressin cells. Moreover, we discovered that the experimental condition p27Kip1+TGFbeta induced 12 migration genes and repressed 7 genes whereas mock-transfected cells exposed to TGFbeta increased 2 anti-migration genes and repressed only one.

A new pro-migratory action of TGFbeta in thyroid Papilar Carcinoma suggested by this fingerprint will be discussed.