Pituitary Tumor-Transforming Gene: Physiology and Implications for Tumorigenesis
George Vlotides,
Tamar Eigler and
Shlomo Melmed
Department of Medicine, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles, California 90048
Correspondence: Address all correspondence and requests for reprints to: Shlomo Melmed, Academic Affairs, Room 2015, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: melmed{at}csmc.edu
Pituitary tumor-transforming gene-1 (PTTG1) is overexpressedin a variety of endocrine-related tumors, especially pituitary,thyroid, breast, ovarian, and uterine tumors, as well as nonendocrine-relatedcancers involving the central nervous, pulmonary, and gastrointestinalsystems. Forced PTTG1 expression induces cell transformationin vitro and tumor formation in nude mice. In some tumors, highPTTG1 levels correlate with invasiveness, and PTTG1 has beenidentified as a key signature gene associated with tumor metastasis.Increasing evidence supports a multifunctional role of PTTG1in cell physiology and tumorigenesis. Physiological PTTG1 propertiesinclude securin activity, DNA damage/repair regulation and involvementin organ development and metabolism. Tumorigenic mechanismsfor PTTG1 action involve cell transformation and aneuploidy,apoptosis, and tumorigenic microenvironment feedback. This paperreviews recent advances in our understanding of PTTG1 structureand regulation and addresses known mechanisms of PTTG1 action.Recent knowledge gained from PTTG1-null mouse models and transgenicanimals and their potential application to subcellular therapeutictargeting PTTG1 are discussed.
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