Abstract 3929: Overexpression of ZNF703 may activate Akt1 in NSCLC
Authors: NUR BUYRU, Burak Bakir, Onur Baykara, Kamil Kaynak, Nejat Dalay
Journal: Cancer Research (2015)

Abstract Like most other epithelial malignancies, NSCLC is characterized by a complex karyotypic pattern with multiple, non-randomly gains and deletions of chromosomal segments. Therefore, several investigators have analyzed NSCLC tumors using conventional comperative genomic hybridization (CGH) or fluorescence in situ hybridization (FISH) techniques to identify the chromosomal aberrations. The 8p11-12 region is one of the most frequently rearranged chromosomal regions in the human genome. The region is prone to chromosomal breaks which makes it a candidate region for cancer research. It can contribute to oncogenesis via inactivation of one or multiple potential tumor suppressor genes and/or amplification and overexpression of candidate oncogenes. Four different amplicons have been identified in the 8p11-12 region. The ZNF703, PROSC, BRF2 and RAB11F1P1 genes reside on the telomeric amplicon A1 and are considered as potential drivers of this amplicon. ZNF703 is one of the candidate oncogenes and its amplification and/or overexpression has been associated with luminal type breast cancer. ZNF703 belongs to the NET family zinc-finger transcription factors and its function depends on the cellular context. More recently, it has been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway in breast cancer cell lines. The Akt1 protein can be activated by different pathways and phosphorylation at theSer473 residue is an indicator of activation. In this study we analyzed the copy numbers and expression levels in association with Akt1 phosphorylation levels by MLPA, qRT-PCR and Western blotting, respectively. ZNF703 amplification was detected in 46.3% of the tumor tissue samples compared to adjacent non-cancerous tissues. When we analyzed the mRNA expression levels of the ZNF703 gene in the tumor samples we observed overexpression in 28 (59.6%) of the samples. We also investigated phosphorylation of the Akt protein in 43 tumor samples in association with ZNF703 expression. An increase in Akt phosphorylation was observed in 51.1% of the tumor tissue samples. When we correlated Akt1 phosphorylation with CNV and ZNF703 mRNA expression levels, the increase of p-Akt1 was more frequent in the samples displaying ZNF703 gene amplification and overexpression. However, this positive association was not statistically significant (p = 0.07). On the other hand, when association of ZNF703 expression and Akt1 phoshorylation levels with clinicopathological parameters were analyzed, higher ZNF703 mRNA levels were observed in SCC tumors compared to adenocarcinomas (p = 0.05). Our results indicate that ZNF703 may contribute to the development of SSCs by activating the Akt signaling pathway. Citation Format: NUR BUYRU, Burak Bakir, Onur Baykara, Kamil Kaynak, Nejat Dalay. Overexpression of ZNF703 may activate Akt1 in NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3929. doi:10.1158/1538-7445.AM2015-3929