Electromagnetic fields at mobile phone frequency induce apoptosis and inactivation of the multi-chaperone complex in human epidermoid cancer cells

2005 ◽  
Vol 204 (2) ◽  
pp. 539-548 ◽  
Author(s):  
Michele Caraglia ◽  
Monica Marra ◽  
Fabrizio Mancinelli ◽  
Guglielmo D'ambrosio ◽  
Rita Massa ◽  
...  
2010 ◽  
Vol 30 (5) ◽  
pp. 1243-1253 ◽  
Author(s):  
Li Ni ◽  
Chun-Song Yang ◽  
Daniel Gioeli ◽  
Henry Frierson ◽  
David O. Toft ◽  
...  

ABSTRACT Prostate cancer progression to the androgen-independent (AI) state involves acquisition of pathways that allow tumor growth under low-androgen conditions. We hypothesized that expression of molecular chaperones that modulate androgen binding to AR might be altered in prostate cancer and contribute to progression to the AI state. Here, we report that the Hsp90 cochaperone FKBP51 is upregulated in LAPC-4 AI tumors grown in castrated mice and describe a molecular mechanism by which FKBP51 regulates AR activity. Using recombinant proteins, we show that FKBP51 stimulates recruitment of the cochaperone p23 to the ATP-bound form of Hsp90, forming an FKBP51-Hsp90-p23 superchaperone complex. In cells, FKBP51 expression promotes superchaperone complex association with AR and increases the number of AR molecules that undergo androgen binding. FKBP51 stimulates androgen-dependent transcription and cell growth, and FKBP51 is part of a positive feedback loop that is regulated by AR and androgen. Finally, depleting FKBP51 levels by short hairpin RNA reduces the transcript levels of genes regulated by AR and androgen. Because the superchaperone complex plays a critical role in determining the ligand-binding competence and transcription function of AR, it provides an attractive target for inhibiting AR activity in prostate cancer cells.


2001 ◽  
Vol 64 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Lijun Pang ◽  
Cristina Baciu ◽  
Nelly Traitcheva ◽  
Hermann Berg

2007 ◽  
Vol 405 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Joseph Friedman ◽  
Sarah Kraus ◽  
Yirmi Hauptman ◽  
Yoni Schiff ◽  
Rony Seger

The exposure to non-thermal microwave electromagnetic fields generated by mobile phones affects the expression of many proteins. This effect on transcription and protein stability can be mediated by the MAPK (mitogen-activated protein kinase) cascades, which serve as central signalling pathways and govern essentially all stimulated cellular processes. Indeed, long-term exposure of cells to mobile phone irradiation results in the activation of p38 as well as the ERK (extracellular-signal-regulated kinase) MAPKs. In the present study, we have studied the immediate effect of irradiation on the MAPK cascades, and found that ERKs, but not stress-related MAPKs, are rapidly activated in response to various frequencies and intensities. Using signalling inhibitors, we delineated the mechanism that is involved in this activation. We found that the first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS (reactive oxygen species). These ROS then directly stimulate MMPs (matrix metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor, which in turn further activates the ERK cascade. Thus this study demonstrates for the first time a detailed molecular mechanism by which electromagnetic irradiation from mobile phones induces the activation of the ERK cascade and thereby induces transcription and other cellular processes.


2004 ◽  
Vol 93 (1) ◽  
pp. 188-196 ◽  
Author(s):  
Fabrizio Mancinelli ◽  
Michele Caraglia ◽  
Alberto Abbruzzese ◽  
Guglielmo d'Ambrosio ◽  
Rita Massa ◽  
...  

2008 ◽  
Vol 29 (6) ◽  
pp. 488-497 ◽  
Author(s):  
H. Kleinlogel ◽  
Th. Dierks ◽  
Th. Koenig ◽  
H. Lehmann ◽  
A. Minder ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document