GLI1 upregulates C-JUN through a specific 130-kDa isoform

Amable,Lauren; Gavin,Elaine; Kudo,Kenji; Meng,Erhong; Rocconi,Rodney P.; Shevde,Lalita A.; Reed,Eddie

doi:10.3892/ijo.2013.2222

GLI1 upregulates C-JUN through a specific 130-kDa isoform

Authors:
- Lauren Amable
- Elaine Gavin
- Kenji Kudo
- Erhong Meng
- Rodney P. Rocconi
- Lalita A. Shevde
- Eddie Reed
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Affiliations: National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892, USA, Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA, Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Published online on: December 20, 2013 https://doi.org/10.3892/ijo.2013.2222
Pages: 655-661
Copyright: © Amable et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The Hedgehog pathway is molecularly linked to increased resistance to cisplatin and increased repair of platinum-DNA damage, through C-JUN. GLI1, which has five known isoforms, is a positive transcriptional regulator in Hedgehog. Southwestern blot assay, EMSA and ChIP assays indicate that only one of five isoforms of GLI1 may be responsible for the Hedgehog link with C-JUN and thus, increased platinum-DNA adduct repair. Cancer tissues express this 130-kDa isoform at levels 6-fold higher than non-malignant tissues; and this isoform exists in abundance in six of seven ovarian cancer cell lines examined.

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1.	Liao X, Siu MK, Au CW, et al: Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis. 30:131–140. 2009. View Article : Google Scholar : PubMed/NCBI
2.	Chen X, Horiuchi A, Kikuchi N, et al: Hedgehog signal pathway is activated in ovarian carcinomas, correlating with cell proliferation: it’s inhibition leads to growth suppression and apoptosis. Cancer Sci. 98:68–76. 2007.PubMed/NCBI
3.	Ray A, Meng E, Reed E, Shevde LA and Rocconi RP: Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int J Oncol. 39:797–804. 2011.PubMed/NCBI
4.	Mas C and Ruiz i Altaba A: Small molecule modulation of HH-GLI signaling: current leads, trials and tribulations. Biochem Pharmacol. 80:712–723. 2010. View Article : Google Scholar : PubMed/NCBI
5.	Stecca B and Ruiz IAA: Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J Mol Cell Biol. 2:84–95. 2010. View Article : Google Scholar : PubMed/NCBI
6.	Zhu H and Lo HW: The human glioma-associated oncogene homolog 1 (GLI1) family of transcription factors in gene regulation and diseases. Curr Genomics. 11:238–245. 2010. View Article : Google Scholar : PubMed/NCBI
7.	Mine T, Matsueda S, Gao H, et al: Created Gli-1 duplex short-RNA (i-Gli-RNA) eliminates CD44 Hi progenitors of taxol-resistant ovarian cancer cells. Oncol Rep. 23:1537–1543. 2010.PubMed/NCBI
8.	Steg AD, Bevis KS, Katre AA, et al: Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res. 18:869–881. 2012. View Article : Google Scholar : PubMed/NCBI
9.	Kudo K, Gavin E, Das S, Amable L, Shevde LA and Reed E: Inhibition of Gli1 results in altered c-Jun activation, inhibition of cisplatin-induced upregulation of ERCC1, XPD and XRCC1 and inhibition of platinum-DNA adduct repair. Oncogene. 31:4718–4724. 2012. View Article : Google Scholar : PubMed/NCBI
10.	Zhong X, Thornton K and Reed E: Computer based analyses of the 5′-flanking regions of selected genes involved in the nucleotide excision repair complex. Int J Oncol. 17:375–380. 2000.
11.	Bonovich M, Olive M, Reed E, O’Connell B and Vinson C: Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell lines. Cancer Gene Ther. 9:62–70. 2002. View Article : Google Scholar : PubMed/NCBI
12.	Li Q, Tsang B, Bostick-Bruton F and Reed E: Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA expression by pharmacological agents in human ovarian carcinoma cells. Biochem Pharmacol. 57:347–353. 1999. View Article : Google Scholar : PubMed/NCBI
13.	Reed E: ERCC1 measurements in clinical oncology. N Engl J Med. 355:1054–1055. 2006. View Article : Google Scholar : PubMed/NCBI
14.	Reed E: DNA damage and repair in translational oncology: an overview. Clin Cancer Res. 16:4511–4516. 2010. View Article : Google Scholar : PubMed/NCBI
15.	Laner-Plamberger S, Kaser A, Paulischta M, Hauser-Kronberger C, Eichberger T and Frischauf AM: Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes. Oncogene. 28:1639–1651. 2009. View Article : Google Scholar : PubMed/NCBI
16.	Li Q, Gardner K, Zhang L, Tsang B, Bostick-Bruton F and Reed E: Cisplatin induction of ERCC-1 mRNA expression in A2780/CP70 human ovarian cancer cells. J Biol Chem. 273:23419–23425. 1998. View Article : Google Scholar : PubMed/NCBI
17.	Raivich G: c-Jun expression, activation and function in neural cell death, inflammation and repair. J Neurochem. 107:898–906. 2008.PubMed/NCBI
18.	Stecca B and Ruiz i Altaba A: A GLI1-p53 inhibitory loop controls neural stem cell and tumour cell numbers. EMBO J. 28:663–676. 2009. View Article : Google Scholar : PubMed/NCBI
19.	Cheng CK, Yeung CM, Hoo RL, Chow BK and Leung PC: Oct-1 is involved in the transcriptional repression of the gonadotropin-releasing hormone receptor gene. Endocrinology. 143:4693–4701. 2002. View Article : Google Scholar : PubMed/NCBI
20.	Ruiz i Altaba A: Gli proteins encode context-dependent positive and negative functions: implications for development and disease. Development. 126:3205–3216. 1999.PubMed/NCBI
21.	Ruiz i Altaba A: Hedgehog signaling and the Gli code in stem cells, cancer and metastases. Sci Signal. 4:pt92011.PubMed/NCBI
22.	Carpenter RL and Lo HW: Identification, functional characterization and pathobiological significance of GLI1 isoforms in human cancers. Vitam Horm. 88:115–140. 2012. View Article : Google Scholar : PubMed/NCBI
23.	Carpenter RL and Lo HW: Hedgehog pathway and GLI1 isoforms in human cancer. Discov Med. 13:105–113. 2012.PubMed/NCBI
24.	Lo HW, Zhu H, Cao X, Aldrich A and Ali-Osman F: A novel splice variant of GLI1 that promotes glioblastoma cell migration and invasion. Cancer Res. 69:6790–6798. 2009. View Article : Google Scholar : PubMed/NCBI
25.	Agyeman A, Mazumdar T and Houghton JA: Regulation of DNA damage following termination of Hedgehog (HH) survival signaling at the level of the GLI genes in human colon cancer. Oncotarget. 3:854–868. 2012.PubMed/NCBI
26.	Leonard JM, Ye H, Wetmore C and Karnitz LM: Sonic Hedgehog signaling impairs ionizing radiation-induced checkpoint activation and induces genomic instability. J Cell Biol. 183:385–391. 2008. View Article : Google Scholar : PubMed/NCBI