Co-chaperones of the Mammalian Endoplasmic Reticulum - The Networking of Chaperones by Co-chaperones - page 191

quantitative real-time PCR revealed that the SEC62 gene had the highest known
amplification frequency (50 %) in prostate cancer and was found to be up-regulated
at the mRNA and protein level in all tumors analyzed (Jung et al. 2006 ). Recently,
this was also observed for cancers of the lung and thyroid (Greiner et al. 2011a ,
2011b ; Linxweiler et al. 2012 , 2013 ) and SEC62 ( TLOC1 ) was characterized as a
cancer driver gene (Hagenstrand et al. 2013 ). Thus, SEC62 over-expression appears
to be associated with a proliferative advantage for various cancer cells, which ap-
pears to be due to the role of Sec62 in cellular calcium homeostasis. In summary, a
Sec62-Sec63 imbalance is likely to contribute to the development of various human
malignancies.
A common theme seems to emerge from some of the described patho-physio-
logical situations in mice and men (summarized in Table 9.1 ): Mammalian cells,
which are highly active in protein secretion, may be particularly sensitive towards
problems in Sec61 channel closure and, therefore, constantly on the verge to apop-
tosis, e.g. seen in the ʲ-cells of the mouse with the Sec61αY344H mutation. On the
other hand, the secretory active cells may be particularly sensitive to imbalances in
the Sec62 to Sec63 ratio, which result in over-efficient Sec61 channel closure and,
thus, a proliferative advantage that can lead to cancer, e.g. seen after over-epression
of SEC62 in prostate or lung cancer. However, it remains to be seen to what extent
the other diseases that are listed in Table 9.1 fit into this scheme.
Acknowledgements We are grateful to Drs Roland Beckmann (Munich), Gregory L. Blatch
(Melbourne, Australia), Adolfo Cavali￩ (Homburg), Johanna Dudek (Homburg), Friedrich F￶rster
(Martinsried), Markus Greiner (Homburg), Volkhard Helms (Saarbrcken), Stephen High (Man-
chester, UK), Martin Jung (Homburg), James C. Paton (Adelaide, Australia) Stefan Pfeffer (Mar-
tinsried), Albert Sickmann (Dortmund), J￶rg Tatzelt (Bochum), Richard Wagner (Osnabrck), and
Ren￩ P. Zahedi (Dortmund) for many years of fruitful collaborations. This work was supported by
the Deutsche Forschungsgemeinschaft (DFG).
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