Genechip Microarray analysis of pituitary adenomas developed by HMGA transgenic mice

The HMGA proteins have been associated with the neoplastic phenotype in various malignant and benign tumours. They play a crucial role in the process of tumorigenesis through a mechanism still unknown. The ubiquitous expression of either HMGA1 or HMGA2 proteins in mice causes the onset of pituitary adenomas secreting growth hormone and prolactin, suggesting a key role of the HMGA proteins in this particular kind of tumor. This is consistent with our recent results showing amplification and overexpression of the HMGA2 gene in a large set of human prolactinomas. To investigate the mechanism by which HMGA proteins are involved in pituitary tumorigenesis we characterized, through genechip microarrays Affymetrix, the gene expression changes associated to the HMGA-induced pituitary adenomas in comparison with normal pituitary glands from wild-type mice. We identified a cohort of about 100 genes whose expression was specifically changed at least 5-fold in pituitary adenomas compared with normal gland. Some of them resulted specifically changed also in human pituitary adenomas and in a panel of rat and mouse cell lines representative of the different pituitary adenoma histotypes. In particular, we focused on two genes, the Melanoma Inhibitor Activity (MIA) and the Cyclyn B2 (cycB2) genes, that were under-expressed and over-expressed in pituitary adenomas vs pituitary gland, respectively, and found that both of them were directly regulated by the HMGA proteins.