Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite therapeutic advances, lung cancer remains one of the most common causes of cancer-related deaths worldwide. The ZNF703 gene has been identified as the driver of the 8p11-12 region and its amplification or overexpression has been associated with several types of cancers. It has also been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway. The aim of our study was to investigate the role of the ZNF703 gene in association with Akt/mTOR activation in non-small cell lung cancer (NSCLC). Expression levels in tumors and matched noncancerous tissue samples from 47 patients were analyzed by qRT-PCR and the Akt phosphorylation levels were investigated by Western blotting. Our results show that ZNF703 is up-regulated in 63.4% of NSCLC tumor samples. Althogh the correlation did not reach a statistically significant level Akt phosphorylation was increased in tumor tissues expressing high levels of ZNF703. The role of the ZNF703 gene has not been investigated in NSCLC. Our data show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway.
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PMID:ZNF703 Overexpression may act as an oncogene in non-small cell lung cancer. 2765 Apr 86

Zinc finger protein 703 (ZNF703) is a new member of the zinc finger protein family of transcription factors that plays an important role during embryogenesis in metazoans. The overexpression of ZNF703 contributes to tumorigenesis and progression of a number of malignancies by activating the Akt/mammalian target of rapamycin (mTOR) signaling pathway. This pathway is activated in medullary thyroid cancer (MTC), but its mechanism of action is not yet fully understood. The aim of the present study was to examine the role of ZNF703 and its association with Akt/mTOR activation in MTC. The present study used the phosphorylation of Akt1 protein at serine 473 (pAkt473) as an indicator of signaling activation. Immunohistochemistry (IHC) staining and western blot analyses were performed in order to examine the expression of ZNF703 in 34 cases of MTC and 12 cases of corresponding normal thyroid tissues. ZNF703 expression in MTC was significantly higher compared with the corresponding normal thyroid tissues (P<0.05). Furthermore, expression of ZNF703 was associated with tumor size, lymph node metastasis and advanced stage of disease. IHC also demonstrated that the level of ZNF703 was positively correlated with p-Akt473 in the 34 cases of MTC. The human MTC cell line TT was selected for further investigation as TT cells exhibit Akt/mTOR activation. The biological effects of silencing ZNF703 in TT cells on proliferation and apoptosis, both in vitro and in vivo were investigated in the present study. ZNF703 silencing inhibited the proliferation of TT cells in vitro and inhibited xenograft tumor growth in vivo. These effects were accompanied by the substantial decrease of pAkt473 and the induction of p53 protein. These results demonstrate that ZNF703 may play a relevant role in MTC due to its association with the Akt/mTOR signaling pathway.
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PMID:Silencing of zinc finger protein 703 inhibits medullary thyroid carcinoma cell proliferation in vitro and in vivo. 3189 7