Researcher at the Italian National Research Council (CNR) Istituto di Endocrinologia e Oncologia Sperimentale ‘G. Salvatore’, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare ‘L. Califano’, Università di Napoli Federico II

Research
The research interests of the group have concentrated on cell cycle regulation in thyroid and breast epithelium cells and on the molecular changes that occur in the corresponding cancers. The group has shown that the cyclin-dependent kinase inhibitor p27Kip1 plays a crucial role in the growth regulation of thyroid cells. In fact, they identified a novel mechanism whereby the growth-inhibitory activity of p27Kip1 is overcome in cancer cells: cytoplasmic retention. Finally, they helped to demonstrate that in thyrocytes, p27Kip1 is a key molecular target on which impinge such mitogenic signaling pathways as PTEN/PI3K/Akt and rPTPη/MAPK.
Future aims of the laboratory are to gain a better understanding of the pathways whereby the PTEN/PI3K/Akt pathway regulates cell proliferation and transformation, with particular attention on the signaling mechanisms that promote cell cycle and apoptosis of breast and thyroid cells. They are investigating whether direct phosphorylation of p27Kip1 and p21Cip1 CDK inhibitors by Akt and other kinases regulates their localization and function, and the role of scaffold proteins (i.e. those of the 14.3.3 family) in determining the localization and activity of Cip/Kip CDK inhibitors. The aim is to generate transgenic mice that express activated Akt-1 targeted to the thyroid gland, to investigate the molecular effects exerted by the constitutive activation of this signaling pathway in in vitro cell culture and in in vivo models. In parallel with these studies, they will try to isolate novel cyclin/CDK interactors by the yeast 2 hybrid strategy.

Selected publications

Trapasso F, Iuliano R, Boccia A, Stella A, Visconti R, Bruni P, Baldassarre G, Santoro M, Viglietto G, Fusco A. Tumor suppressor activity of the rat protein tyrosine phosphatase η through stabilization of the p27kip1 protein. Mol Cell Biol 2000;20:9236-46.

Bruni P, Baldassarre G, Boccia A, Trapasso F, Santoro M, Chiappetta G, Fusco A, Viglietto G. The expression of the tumor suppressor gene PTEN is reduced in a subset of sporadic thyroid carcinomas: evidence that growth-suppressing activity in thyroid cancer cells is mediated by p27kip1. Oncogene 2000;19:3146-55.

Baldassarre G, Barone MV, Belletti B, Sandomenico C, Bruni P, Spiezia S, Boccia A, Vento MT, Romano A, Pepe S, Fusco A and Viglietto G. Key role of the cyclin-dependent kinase inhibitor p27^kip1 for embrional carcinoma cell survival and differentiation. Oncogene 1999;18:6241-51.

Baldassarre G, Belletti B, Bruni P, Boccia A, Trapasso F, Pentimalli F, Barone MV, Chiappetta G, Vento MT, Spiezia S, Fusco A, Viglietto G. Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells. J Clin Invest 1999;10:865-74.