Gene amplification alters gene expression and can promote oncogenesis. In particular, the amplification of chromosome 19q13.1-13.2 has been found in several cancers and is known to contain the AKT2 oncogene. Two members of the SERTAD gene family of transcription factors, SERTAD1 and SERTAD3, are also located within this region. We report herein the genomic structure, regulation, and functions of SERTAD3. This gene has two transcript variants with short mRNA half-lives, and one of the variants is tightly regulated throughout G1 and S phases of the cell cycle. Overexpression of SERTAD3 induces cell transformation in vitro and tumor formation in mice, while inhibition of SERTAD3 by siRNA results in a 2-4 fold reduction in cell growth rate. Furthermore, luciferase assays based on E2F-1 binding indicate that SERTAD3 increases the activity of E2F, which can be strongly reduced by siRNA inhibition of SERTAD3. Together, our data support that SERTAD3 contributes to oncogenesis at least in part via an E2F-dependent mechanism.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.100790 |
| Date | January 2006 |
| Creators | Darwish, Hanni. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | © Hanni Darwish, 2006 |
| Relation | alephsysno: 002586677, proquestno: AAIMR32686, Theses scanned by UMI/ProQuest. |
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