Pituitary neoplasms are associated with a great deal off morbidity of excessive hormone production and/or as space occupying lesions in the central nervous system. The mechanisms regulating pituitary tumor growth in humans are poorly understood. Recent studies have shown that pituitary adenomas are monoclonal and that some specific genetic alterations are present in these tumors. However, very little is known about the regulation of the pituitary tumor growth and why only few of these neoplasms become malignant, which usually leads to the patient's demise in spite of aggressive treatment. Our laboratory has recently developed human pituitary cell lines immortalized with a replication-defective recombinant human adenovirus which should provide stable cell lined for many of the proposed studies. We plan to examine the mechanisms regulating pituitary growth and tumor progression using cell and molecular biological approaches. Preliminary studies indicate that pancreastain, a proteolytic product of chromogranin, which is processed by PC 1/3 and PC 2 in pituitary cells, has autocrine and paracrine regulatory functions on pituitary tumor cells. Our preliminary studies also showed that pancreastain inhabits cell proliferation in vitro. The haploid insufficiency paradigm will be explored to possibly explain some of the effects of p27 on pituitary tumor development and progression. Our laboratory was the first to discover leptin production and secretion by anterior pituitary cells. We also noted that leptin inhabit plan to examine the mechanism of leptin action in the pituitary.
The specific aims i nclude: I. Determine the role of chromogranin/secretogranin proteolytic products and neuroendocrine-specific proconvertases in pituitary tumor growth and differentiation. II. Determine the role of specific cell cycle inhibitors in the development of pituitary tumors. a. Examine the mechanism regulating p27 expression in pituitary tumor development and progression. b. Determine the role of p16 methylation in pituitary tumor development. III. Examine the role of leptin, leptin receptors, STAT and SOCS proteins in pituitary tumor development and progression. The information derived from these studies should provide insight into the pathobiology of pituitary tumors and lead to more effective treatment modalities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090249-04
Application #
6745632
Study Section
Special Emphasis Panel (ZRG1-ET-2 (01))
Program Officer
Sussman, Daniel J
Project Start
2001-05-15
Project End
2006-04-30
Budget Start
2004-05-01
Budget End
2005-04-30
Support Year
4
Fiscal Year
2004
Total Cost
$234,226
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Hardin, Heather; Helein, Holly; Meyer, Kristy et al. (2018) Thyroid cancer stem-like cell exosomes: regulation of EMT via transfer of lncRNAs. Lab Invest 98:1133-1142
Zhang, Ranran; Hardin, Heather; Huang, Wei et al. (2017) MALAT1 Long Non-coding RNA Expression in Thyroid Tissues: Analysis by In Situ Hybridization and Real-Time PCR. Endocr Pathol 28:7-12
Xu, Jin; Hardin, Heather; Zhang, Ranran et al. (2016) Stage-Specific Embryonic Antigen-1 (SSEA-1) Expression in Thyroid Tissues. Endocr Pathol 27:271-275
Chung, Bowen; Ong, Michael; Ettner, Susan L et al. (2014) 12-month outcomes of community engagement versus technical assistance to implement depression collaborative care: a partnered, cluster, randomized, comparative effectiveness trial. Ann Intern Med 161:S23-34
Montemayor-Garcia, Celina; Hardin, Heather; Guo, Zhenying et al. (2013) The role of epithelial mesenchymal transition markers in thyroid carcinoma progression. Endocr Pathol 24:206-12
Ruebel, Katharina; Leontovich, Alexey A; Stilling, Gail A et al. (2010) MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression. Mod Pathol 23:367-75
Zhang, He-Yu; Jin, Long; Stilling, Gail A et al. (2009) RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors. Endocrine 35:101-11
Ruebel, Katharina H; Leontovich, Alexey A; Tanizaki, Yoshinori et al. (2008) Effects of TGFbeta1 on gene expression in the HP75 human pituitary tumor cell line identified by gene expression profiling. Endocrine 33:62-76
Ruebel, Katharina H; Leontovich, Alexey A; Jin, Long et al. (2006) Patterns of gene expression in pituitary carcinomas and adenomas analyzed by high-density oligonucleotide arrays, reverse transcriptase-quantitative PCR, and protein expression. Endocrine 29:435-44
Lombardero, Matilde; Vidal, Sergio; Hurta, Robert et al. (2006) Modulation of VEGF/Flk-1 receptor expression in the rat pituitary GH3 cell line by growth factors. Pituitary 9:137-43

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