In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 1086-1086
Abstract:
EGF treatment induces the translocation of its receptor (i.e. EGFR) from the cell surface into the nucleus. Nuclear expression of EGFR is negatively correlated with overall survival of cancer patients and EGFR nuclear translocation is important for cancer cell's resistance to the treatment with Cetuximab, cisplatin and radiation. Moreover, EGFR in the nucleus can associates with other proteins including STAT3, STAT5A, DNA-PK and PCNA to regulate cell transformation, proliferation, and DNA repair and replication. It has been demonstrated that nuclear EGFR regulates gene transcription through its binding to an AT-rich sequence (ATRS) of target gene promoter. However, EGFR does not have a DNA-binding domain and there is no evidence to support the direct binding of EGFR to the specific DNA sequence. Thus, identification of a DNA-binding partner of nuclear EGFR is crucial for us to understand how EGFR regulates gene transcription in the nucleus. Using a non-biased approach, we identified RNA helicase A (i.e. RHA), which is a highly conserved, multiple functional transcriptional activator, could interact with nuclear EGFR upon EGF stimulation in several cancer cells. The EGFR/RHA complex then associated with gene promoter through binding of RHA to the AT-rich sequence of the promoter to activate its transcription. Knockdown of RHA expression was found to abrogate the binding of EGFR to its target gene promoter, thereby reducing EGF/EGFR-induced gene expression. Moreover, interruption of EGFR-RHA interaction decreased EGFR-induced promoter activity. Interestingly, we found that the EGFR/RHA-regulated gene promoter activity is dependent on the EGFR tyrosine kinase activity but independent of RHA helicase activity. Finally, we observed a positive correlation among nuclear expression of EGFR, RHA and cyclin D1 in human breast cancer tissue samples. These results, taken together, indicate that RHA is an important mediator for EGFR-induced gene transactivation in cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1086. doi:10.1158/1538-7445.AM2011-1086
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-1086
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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