Inscrição na biblioteca: Guest
Portal Digital Begell Biblioteca digital da Begell eBooks Diários Referências e Anais Coleções de pesquisa
Critical Reviews™ in Immunology
Fator do impacto: 1.404 FI de cinco anos: 3.347 SJR: 0.706 SNIP: 0.55 CiteScore™: 2.19

ISSN Imprimir: 1040-8401
ISSN On-line: 2162-6472

Volumes:
Volume 40, 2020 Volume 39, 2019 Volume 38, 2018 Volume 37, 2017 Volume 36, 2016 Volume 35, 2015 Volume 34, 2014 Volume 33, 2013 Volume 32, 2012 Volume 31, 2011 Volume 30, 2010 Volume 29, 2009 Volume 28, 2008 Volume 27, 2007 Volume 26, 2006 Volume 25, 2005 Volume 24, 2004 Volume 23, 2003 Volume 22, 2002 Volume 21, 2001 Volume 20, 2000 Volume 19, 1999 Volume 18, 1998 Volume 17, 1997 Volume 16, 1996 Volume 15, 1995 Volume 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v21.i1-3.180
12 pages

Targeting the ATF-1/CREB Transcription Factors by Single Chain Fv Fragment in Human Melanoma: Potential Modality for Cancer Therapy

Didier Jean
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX
Menashe Bar-Eli
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

RESUMO

Activating transcription factor-1 (ATF-1) and cAMP-responsive element (CRE)-binding protein (CREB) have been implicated in cAMP and Ca2+-induced transcriptional activation. The expression of the transcription factors ATF-1 and CREB is upregulated in metastatic melanoma cells. However, how overexpression of ATF-1/CREB contributes to the acquisition of the metastatic phenotype is unclear. Previously we demonstrated that quenching of CREB activity in metastatic melanoma cells by means of a dominant-negative form of CREB (KCREB) led to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain how overexpression of CREB/ATF-1 contributes to the metastatic phenotype. The first is one in which CREB/ATF-1 play an essential role in invasion by regulating the CREdependent expression of the metalloproteinase MMP-2 and the adhesion molecule MCAM/MUC18 genes. In the second mechanism, CREB and ATF-1 act as survival factors for human melanoma cells. Here, the effect of disrupting ATF-1 activity was investigated using intracellular expression of an inhibitory anti-ATF-1 single chain antibody fragment (ScFv). Intracellular expression of ScFv anti-ATF-1 in MeWo melanoma cells caused significant reduction in CRE-dependent promoter activation. In addition, expression of ScFv anti-ATF-1 in melanoma cells suppressed their tumorigenicity and metastatic potential in nude mice. ScFv anti-ATF-1 rendered the melanoma cells susceptible to thapsigargin-induced apoptosis in vitro and caused massive apoptosis in tumors transplanted subcutaneously into nude mice, confirming that AFT-1/CREB act as survival factors for human melanoma cells. These studies demonstrate the potential usage of ScFv anti-ATF-1 as an inhibitor of tumor growth and metastasis of solid tumors in vivo.


Articles with similar content:

Mechanisms of p53-Mediated Apoptosis
Critical Reviews™ in Oncogenesis, Vol.9, 1998, issue 1
Han-Fei Ding, David E. Fisher
Tyrosine Kinase Inhibitor AG490 Inhibits the Proliferation and Migration and Disrupts Actin Organization of Cancer Cells
Journal of Environmental Pathology, Toxicology and Oncology, Vol.32, 2013, issue 4
Kavita Shirsath, Rajiv P. Gude, Prachi Patil, Mohammad Zahid Kamran
KLF4 in Ovarian Cancer
Onco Therapeutics, Vol.7, 2016, issue 1-2
Lawrence M. Pfeffer, Baojin Wang, Ziyun Du, Junming Yue
Oleanolic acid induces Apoptosis by modulating p53, Bax, Bcl-2 and caspase-3 gene expression and regulates the activation of transcription factors and cytokine profile in B16F
Journal of Environmental Pathology, Toxicology and Oncology, Vol.30, 2011, issue 1
P. Pratheeshkumar, Girija Kuttan
Influence of the Inhibitor of Nf-KB Activation, Curcumin, on the Oogenesis and Follicular Cell Death under Immune Ovarian Failure in Mice
International Journal of Physiology and Pathophysiology, Vol.2, 2011, issue 2
Irina N. Alexeyeva, Vera S. Sukhina, Tetyana M. Bryzgina, Tetyana Yu. Voznesenska, Nataliya V. Makogon