scholarly journals Expression of transcription factor CREB1 in human breast cancer and its correlation with prognosis

Author(s):  
Alok Chhabra ◽  
Herman Fernando ◽  
Gareth Watkins ◽  
Robert Mansel ◽  
Wen Jiang
2004 ◽  
Vol 24 (12) ◽  
pp. 5548-5564 ◽  
Author(s):  
Jason D. Prescott ◽  
Karen S. N. Koto ◽  
Meenakshi Singh ◽  
Arthur Gutierrez-Hartmann

ABSTRACT Several different transcription factors, including estrogen receptor, progesterone receptor, and ETS family members, have been implicated in human breast cancer, indicating that transcription factor-induced alterations in gene expression underlie mammary cell transformation. ESE-1 is an epithelium-specific ETS transcription factor that contains two distinguishing domains, a serine- and aspartic acid-rich (SAR) domain and an AT hook domain. ESE-1 is abundantly expressed in human breast cancer and trans-activates epithelium-specific gene promoters in transient transfection assays. While it has been presumed that ETS factors transform mammary epithelial cells via their nuclear transcriptional functions, here we show (i) that ESE-1 protein is cytoplasmic in human breast cancer cells; (ii) that stably expressed green fluorescent protein-ESE-1 transforms MCF-12A human mammary epithelial cells; and (iii) that the ESE-1 SAR domain, acting in the cytoplasm, is necessary and sufficient to mediate this transformation. Deletion of transcriptional regulatory or nuclear localization domains does not impair ESE-1-mediated transformation, whereas fusing the simian virus 40 T-antigen nuclear localization signal to various ESE-1 constructs, including the SAR domain alone, inhibits their transforming capacity. Finally, we show that the nuclear localization of ESE-1 protein induces apoptosis in nontransformed mammary epithelial cells via a transcription-dependent mechanism. Together, our studies reveal two distinct ESE-1 functions, apoptosis and transformation, where the ESE-1 transcription activation domain contributes to apoptosis and the SAR domain mediates transformation via a novel nonnuclear, nontranscriptional mechanism. These studies not only describe a unique ETS factor transformation mechanism but also establish a new paradigm for cell transformation in general.


Oncogene ◽  
2002 ◽  
Vol 21 (43) ◽  
pp. 6567-6572 ◽  
Author(s):  
Ceshi Chen ◽  
Hina V Bhalala ◽  
Hui Qiao ◽  
Jin-Tang Dong

2005 ◽  
Vol 118 (4) ◽  
pp. 869-878 ◽  
Author(s):  
Laila Samady ◽  
David J. Faulkes ◽  
Vishwanie Budhram-Mahadeo ◽  
Daniel Ndisang ◽  
Eyck Potter ◽  
...  

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