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Department of Medicine, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles, California 90048, USA
* To whom correspondence should be addressed. E-mail: melmed{at}csmc.edu.
Pituitary tumor transforming gene-1 (PTTG1) is over-expressed in a variety of endocrine-related tumors, especially pituitary, thyroid, breast, ovarian and uterine tumors, as well as non-endocrine related cancers, involving the CNS, pulmonary, and gastrointestinal system. Forced PTTG1 expression induces cell transformation in vitro and tumor formation in nude mice. In some tumors, high PTTG1 levels correlate with invasiveness, and PTTG1 has been identified as a key signature gene associated with tumor metastasis. Increasing evidence supports a multi-functional role of PTTG1 in cell physiology and tumorigenesis. Physiologic PTTG1 properties include securin activity, DNA damage/repair regulation and involvement in organ development and metabolism. Tumorigenic mechanisms for PTTG1 action involve cell transformation and aneuploidy, apoptosis and tumorigenic microenvironment feedback. This paper reviews recent advances in our understanding PTTG1 structure and regulation, and addresses known mechanisms of PTTG1 action. Recent knowledge gained from PTTG1-null mouse models and transgenic animals, as well as their potential application to subcellular therapeutic targeting PTTG1 are discussed.
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