Evidence that corticotropin-releasing hormone inhibits cell growth of human breast cancer cells via the activation of CRH-R1 receptor subtype

2007 ◽  
Vol 264 (1-2) ◽  
pp. 44-49 ◽  
Author(s):  
Grazia Graziani ◽  
Lucio Tentori ◽  
Alessia Muzi ◽  
Matteo Vergati ◽  
Giuseppe Tringali ◽  
...  
2003 ◽  
Vol 17 (10) ◽  
pp. 2002-2012 ◽  
Author(s):  
Olga A. Sukocheva ◽  
Lijun Wang ◽  
Nathaniel Albanese ◽  
Stuart M. Pitson ◽  
Mathew A. Vadas ◽  
...  

Abstract Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17β-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells.


2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Nien‐Tsu Hsieh ◽  
Chun‐Yin Huang ◽  
Yu‐Hsuan Chou ◽  
Wong Ching Ung ◽  
Ming‐Fen Lee

Nature ◽  
1985 ◽  
Vol 313 (5999) ◽  
pp. 231-233 ◽  
Author(s):  
W. R. Miller ◽  
W. N. Scott ◽  
R. Morris ◽  
H. M. Fraser ◽  
R. M. Sharpe

2010 ◽  
Vol 285 (49) ◽  
pp. 38093-38103 ◽  
Author(s):  
Osamu Ikeda ◽  
Yuichi Sekine ◽  
Akihiro Mizushima ◽  
Misa Nakasuji ◽  
Yuto Miyasaka ◽  
...  

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