Abstract
Reprimo (RPRM), initially identified as a downstream effector of p53-induced cell cycle arrest at G(2)/M, is a putative tumor suppressor silenced in some types of cancer. In microarrays, the RPRM transcript was repressed 26-fold in gonadotrope (null cell) human pituitary tumors compared with normal pituitary but in the absence of changes in p53. Inhibition of RPRM mRNA was confirmed by RT-PCR in all gonadotrope tumors, most GH samples, and variably in other tumor types. Human pituitary tumors showed no evidence of abnormal promoter hypermethylation as a mechanism of RPRM repression. RPRM stable expression in gonadotrope (LβT2) and GH (GH3) pituitary cells resulted in decreased rates of cell proliferation by 55 and 30%, respectively; however, RPRM reexpression did not alter G(2)/M transition. In addition, RPRM increased rates of apoptosis in response to growth factor deprivation as assessed by caspase-3 cleavage and nuclear condensation. Clonagenic assays showed a 5.3- and 3.7-fold suppression of colony growth in RPRM-overexpressing LβT2 and GH3 cells, respectively, supporting its role as a tumor suppressor. In cells stably expressing RPRM mRNA, protein levels were actively suppressed due to rapid degradation through ubiquitinat...Continue Reading
References
Jul 1, 1990·The Journal of Clinical Investigation·J M AlexanderA Klibanski
Jun 1, 1996·Genes, Chromosomes & Cancer·T OtsukaJ Yokota
May 15, 1997·Nature·Y HauptM Oren
May 15, 1997·Nature·M H KubbutatK H Vousden
Aug 10, 2000·The Journal of Biological Chemistry·R OhkiT Taniguchi
Apr 21, 2001·Oncogene·W R Taylor, G R Stark
Feb 13, 2002·Journal of Neurosurgery·Björn P MeijEdward R Laws
Mar 13, 2002·The Journal of Clinical Endocrinology and Metabolism·Xun ZhangAnne Klibanski
Nov 7, 2003·The Journal of Clinical Endocrinology and Metabolism·Shereen Ezzat
Nov 7, 2003·The Journal of Clinical Endocrinology and Metabolism·Xun ZhangAnne Klibanski
Dec 9, 2003·The Journal of Clinical Investigation·Shlomo Melmed
Dec 24, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Andreea OlaruStephen J Meltzer
Jul 27, 2004·Cancer·Shereen EzzatIan E McCutcheon
Feb 9, 2005·International Journal of Cancer. Journal International Du Cancer·Takao TakahashiAdi F Gazdar
Feb 17, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Makoto SuzukiAdi F Gazdar
Jun 2, 2005·International Journal of Cancer. Journal International Du Cancer·Thian Sze WongAnthony Po-Wing Yuen
Feb 4, 2006·Molecular Cell·Christopher L Brooks, Wei Gu
Feb 7, 2006·Cancer Letters·Makoto SuzukiEugene P Frenkel
Nov 24, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·James P HamiltonStephen J Meltzer
Dec 2, 2006·Endocrinology·Lynnette Shorts-CaryMargaret E Wierman
Mar 14, 2007·Molecular Systems Biology·Rob M EwingDaniel Figeys
Nov 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mikhail A NikiforovMaria S Soengas
Jan 1, 2009·Endocrinology·Mei XuMargaret E Wierman
Nov 18, 2009·Molecular and Cellular Biology·Simeen MalikSteffi Oesterreich
Aug 4, 2011·Endocrinology·Katherine A MichaelisMargaret E Wierman
Citations
Apr 3, 2014·PloS One·Wei JiangJun Ma
Jan 30, 2015·Leukemia & Lymphoma·Yan-Fang TaoJian Pan
Jan 23, 2016·Biological Research·Kurt BucheggerJuan Carlos Roa
Sep 13, 2015·Experimental Neurology·Yi-Hsin WengHung-Li Wang
Sep 24, 2015·Molecular and Cellular Endocrinology·Katja Kiseljak-VassiliadesMargaret E Wierman
Jan 8, 2014·Endocrinology and Metabolism·Xiaobing Jiang, Xun Zhang
Jul 16, 2015·PloS One·Tao Yan-FangPan Jian
May 9, 2015·PloS One·Kathleen SaavedraAlejandro H Corvalán
Mar 23, 2017·Endocrinology·Katja Kiseljak-VassiliadesMargaret E Wierman
May 27, 2017·Epigenomics·Hanze WangQi Chen
Aug 16, 2017·International Journal of Molecular Sciences·Kurt BucheggerJuan Carlos Roa
Jun 29, 2018·Cancer Medicine·Xueru ZhuXiaolong Fu
Nov 7, 2019·Journal of Cellular Biochemistry·Ze YuChunbo Teng
Mar 22, 2018·Oncotarget·Paulina Cerda-OpazoAndrew F G Quest
Aug 17, 2016·Oncotarget·Benjamin Garcia-BlojPilar Blancafort
Feb 5, 2015·Molecular Endocrinology·Weipeng XiongMargaret E Wierman
Apr 11, 2018·Frontiers in Neuroanatomy·Karen StanicJulio D Amigo
May 11, 2019·Scientific Reports·Karen StanicJulio D Amigo
Jun 14, 2019·Frontiers in Endocrinology·Shehua QianXianquan Zhan
Jun 27, 2018·International Journal of Molecular Sciences·Julio D AmigoAlejandro H Corvalán
Aug 29, 2013·Molecular Cancer Research : MCR·Akira OokiMasahiko Watanabe
Jan 2, 2016·Molecular Cancer Therapeutics·Weipeng XiongMargaret E Wierman
Dec 16, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Jiajia Li, Xianquan Zhan
Jun 29, 2021·Frontiers in Immunology·Tao FanJie He
Jul 14, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Marc Fernandez-GuerreroMarian A Ros
May 12, 2021·Cancer Discovery·Heng PanDan A Landau