Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function, cortisol production and local central pressure effects. Although recently determined to be monoclonal, the genetic mechanisms involved in pituitary cell transformation are unclear. This proposal will characterize the transforming properties of PTTG, a novel pituitary tumor derived protein. We used differential RNA display to identify a rat pituitary derived transforming gene (PTTG) which encodes a 199 a.a. novel protein. Now, we will isolate and study human PTTG and assign its chromosomal locus. PTTG expression will be tested in hormone- secreting (PRL, GH, ACTH) and non-functional pituitary tumors, and its abundance assessed as a function of pituitary adenoma grading, invasinenes, hormonal activity and ultimately long-term clinical outcome. Cellular localization of PTTG will also be determined in these tumors by double immunostaining and in situ techniques. Models of pituitary enlargement (pregnancy and estrogen-induced prolactinomas) will be used to determine PTTG expression in the pathogenesis of the pituicyte to hyperplasia to adenoma formation. PTTG in vitro and in vivo transforming properties will be determined in double agar transformation assays, nude mouse tumorigenesis and growth factor regulation will be assessed. Effects of inducible PTTG expression on cell proliferation will also be assessed. These studies will thus provide mechanistic insight into the pathogenesis of prolactinomas, acromegaly, Cushing's Disease and non-secreting pituitary tumors.
| Melmed, Shlomo (2016) Pituitary Medicine From Discovery to Patient-Focused Outcomes. J Clin Endocrinol Metab 101:769-77 |
| Melmed, Shlomo (2015) Pituitary tumors. Endocrinol Metab Clin North Am 44:1-9 |
| Zhou, Cuiqi; Jiao, Yonghui; Wang, Renzhi et al. (2015) STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion. J Clin Invest 125:1692-702 |
| Cuevas-Ramos, Daniel; Carmichael, John D; Cooper, Odelia et al. (2015) A structural and functional acromegaly classification. J Clin Endocrinol Metab 100:122-31 |
| Ben-Shlomo, Anat; Mirocha, James; Gwin, Stephanie M et al. (2014) Clinical factors associated with biochemical adrenal-cortisol insufficiency in hospitalized patients. Am J Med 127:754-762 |
| Donangelo, Ines; Ren, Song-Guang; Eigler, Tamar et al. (2014) Sca1? murine pituitary adenoma cells show tumor-growth advantage. Endocr Relat Cancer 21:203-16 |
| Carmichael, John D; Bonert, Vivien S; Nuño, Miriam et al. (2014) Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab 99:1825-33 |
| Keeley, Patrick W; Zhou, Cuiqi; Lu, Lu et al. (2014) Pituitary tumor-transforming gene 1 regulates the patterning of retinal mosaics. Proc Natl Acad Sci U S A 111:9295-300 |
| Zhou, C; Tong, Y; Wawrowsky, K et al. (2014) PTTG acts as a STAT3 target gene for colorectal cancer cell growth and motility. Oncogene 33:851-61 |
| Eigler, Tamar; Ben-Shlomo, Anat; Zhou, Cuiqi et al. (2014) Constitutive somatostatin receptor subtype-3 signaling suppresses growth hormone synthesis. Mol Endocrinol 28:554-64 |
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