Overexpression of SERTAD3, a putative oncogene located within the 19q13 amplicon, induces E2F activity and promotes tumor growth.
The amplified region of chromosome 19q13.1-13.2 has been associated with several cancers. The well-characterized oncogene AKT2 is located in this amplicon. Two members of the same gene family (SERTAD1 and SERTAD3) are also located within this region. We report herein the genomic structure and potential functions of SERTAD3. SERTAD3 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, whereas inhibition of SERTAD3 by small interfering RNA (siRNA) results in a reduction in cell growth rate. Furthermore, luciferase assays based on E2F-1 binding indicate that SERTAD3 increases the activity of E2F, which is reduced by inhibition of SERTAD3 by siRNA. Together, our data support that SERTAD3 contributes to oncogenesis, at least in part, via an E2F-dependent mechanism.
Darwish
H
H
Faculty of Medicine, Department of Medicine, Lady Davis Institute for Medical Research and Segal Comprehensive Cancer Center of the Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Cho
J M
JM
Loignon
M
M
Alaoui-Jamali
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D050684:E2F Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology
D050684:E2F Transcription Factors; D015513:Oncogene Proteins; C413405:SERTAD3 protein, human; D015534:Trans-Activators