Abstract
We hypothesize that elevation of nm23-HI metastasis suppressor gene expression in micrometastatic tumor cells may reduce their subsequent colonization and invasion, and induce differentiation, with a clinical benefit. This report presents the first analysis of the nm23-HI promoter to identify sites which can increase its transcription. Deletion mapping of a 2.1 kb nm23-H1 promoter fragment tethered to a reporter gene identified three regions involved in its differential expression levels among a panel of human breast carcinoma cell lines: a 195 bp NheI-XbaI fragment responsible for basal expression levels, a 248 bp AvrII-Nhel fragment which contributed to the elevated nm23-H1 expression observed in the high expressing cell lines, and a 544 bp AvrII fragment containing an inhibitory element. Examination of the 248 bp AvrII-NheI fragment revealed the unexpected presence of three transcription factor binding sites (MAF/Ets, CTF/NF1 half site and ACAAAG enhancer) previously identified in the MMTV-LTR, and in WAP and milk gene promoters, proposed to mediate mammary-specific gene expression. Mutation of the three sites, individually or together, resulted in two-fold reductions in reporter gene expression. As controls, the same panel ...Continue Reading
Citations
Dec 7, 2007·Journal of Cellular and Molecular Medicine·Paraskevi Moutsatsou, Athanasios G Papavassiliou
Apr 24, 2009·Molecular and Cellular Biochemistry·Jean-Claude MarshallPatricia S Steeg
Aug 10, 2011·Leukemia & Lymphoma·Dominic BraunagelUlrich Mahlknech
Sep 27, 2014·Breast Cancer Research and Treatment·Kathy D MillerPatricia S Steeg
Dec 2, 2015·Biomedical Reports·X I HuangShan Kang
Jan 2, 2003·Nature Reviews. Cancer·Patricia S Steeg
Jun 26, 2007·Journal of Mammary Gland Biology and Neoplasia·Kedar S Vaidya, Danny R Welch
Jan 15, 2015·Naunyn-Schmiedeberg's Archives of Pharmacology·Tien HsuUNKNOWN Steering Committee on Nme-related research and the organizers of the International Congresses of the NDP Kinase/Nm23/awd Gen
Feb 27, 2009·Nature Reviews. Cancer·Steven Christopher Smith, Dan Theodorescu
Sep 1, 2006·Journal of Bioenergetics and Biomembranes·Diane PalmieriPatricia S Steeg
Apr 28, 2011·Nature Reviews. Clinical Oncology·Alexander N ShoushtariCarrie W Rinker-Schaeffer
Nov 1, 2011·Leukemia & Lymphoma·Dominic BraunagelUlrich Mahlknecht
Jul 6, 2010·Reproductive Sciences·Chi-Yen FengShun-Fa Yang
Oct 21, 2017·Oncotarget·Yuanjun LiYung H Wong
Aug 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shimian QuWei Zheng
Aug 14, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia S SteegKathy D Miller
Jul 5, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carrie W Rinker-SchaefferDan Theodorescu
Jan 10, 2021·Life Sciences·Liting YuChangying Guo
Feb 19, 2008·The International Journal of Biochemistry & Cell Biology·Lewis J StaffordDanny R Welch
May 15, 2003·Clinical Breast Cancer·Patricia S SteegMassimiliano Salerno
Jul 6, 2010·Gynecologic Oncology·Po-Hui WangShun-Fa Yang