{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:15:54Z","timestamp":1772579754185,"version":"3.50.1"},"reference-count":50,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The genetic and molecular mechanisms that initiate and maintain pituitary tumorigenesis are poorly understood. Nonfunctioning tumors of the gonadotrope lineage represent 35% of all tumors; are usually macroadenomas, often resulting in hypopituitarism; and have no medical treatments. Using expression microarrays combined with whole-genome copy number screens on individual human tumors, we identified the mammalian sterile-20-like kinase (MST4) transcript, which was amplified within chromosome Xq26.2 in one tumor and up-regulated in all gonadotrope tumor samples. MST4 mRNA and protein were consistently overexpressed in human tumors compared with normal pituitaries. To mimic the pituitary tumor microenvironment, a hypoxia model using L\u03b2T2 murine gonadotrope cells was created to examine the functional role of the kinase. During long-term hypoxia, MST4 expression increased colony formation in a soft agar assay and rates of cell proliferation by activating p38 MAPK and AKT. Under short-term severe hypoxic stress, MST4 decreased the rates of apoptosis via p38 MAPK, AKT, hypoxia-inducible factor-1, and its cell-specific downstream targets. Analysis of MST4 mutants confirmed the importance of the kinase sequence but not the regulatory C terminus for its functional effects. Together these data identify the MST4 kinase as a novel candidate to mediate human pituitary tumorigenesis in a hypoxic environment and position it as a potential therapeutic target.<\/jats:p>","DOI":"10.1210\/me.2014-1332","type":"journal-article","created":{"date-parts":[[2015,2,4]],"date-time":"2015-02-04T17:12:24Z","timestamp":1423069944000},"page":"460-472","source":"Crossref","is-referenced-by-count":27,"title":["Mammalian Ste20-Like Kinase 4 Promotes Pituitary Cell Proliferation and Survival Under Hypoxia"],"prefix":"10.1210","volume":"29","author":[{"given":"Weipeng","family":"Xiong","sequence":"first","affiliation":[{"name":"Departments of Medicine (W.X., A.J.K., M.X., K.K.-V., S.P.C., M.E.W.), University of Colorado School of Medicine, Aurora, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron J.","family":"Knox","sequence":"first","affiliation":[{"name":"Departments of Medicine (W.X., A.J.K., M.X., K.K.-V., S.P.C., M.E.W.), University of 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80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelley S.","family":"Brodsky","sequence":"first","affiliation":[{"name":"Anesthesiology (K.S.B.), University of Colorado School of Medicine, Aurora, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bette K.","family":"Kleinschmidt-Demasters","sequence":"first","affiliation":[{"name":"Pathology (B.K.K.-D.), University of Colorado School of Medicine, Aurora, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin O.","family":"Lillehei","sequence":"first","affiliation":[{"name":"Neurosurgery (K.O.L.), University of Colorado School of Medicine, Aurora, Colorado 80045"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret E.","family":"Wierman","sequence":"first","affiliation":[{"name":"Departments of Medicine (W.X., A.J.K., M.X., K.K.-V., S.P.C., M.E.W.), University of Colorado School of Medicine, Aurora, Colorado 80045"},{"name":"Research 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