A protein shown to be present in prostate cancer cells can inhibit the growth of tumours. Called the SOCS-1 protein, it belongs to the SOCS (suppressor of cytokine signalling) class of proteins. These produce very different effects depending on the type of tumour. The work supported by the Austrian Science Fund FWF and now published in the American Journal of Pathology also demonstrates that the growth-inhibiting effect of SOCS-1 is a result of its impact on cell proliferation.
After lung and intestinal cancer, prostate cancer is the form of the disease with the highest mortality rate for men. In the initial stages of tumour development, however, both radiotherapy and surgical removal of tumours offer good prospects for successful treatment. While chemotherapy is increasingly effective at later stages of development, hormone treatment is still currently the method of choice. This is because one of the main reasons for the occurrence and development of the prostate carcinoma is the activation of receptors for male sexual hormones on the prostate cells. In recent years, however, increasing evidence has emerged that chronic inflammation can also be a contributory factor. In order to obtain a better understanding of these relationships, the signalling pathways associated with the process are currently being analysed in detail.
Watch the Signals
The team headed by Prof. Zoran Culig from the Department of Urology at Innsbruck Medical University, Austria, is carrying out research into a very special class of key proteins in these signalling pathways. SOCS – suppressor of cytokine signalling – proteins suppress signals from the cytokines, the key messenger substances in terms of inflammation. As Prof. Culig explains, “At present, we are aware of seven different SOCS proteins that are found in tumour cells in different types of cancer. We have now also been able to provide clear evidence of SOCS-1 in prostate cancer cells. In addition to six different cell lines, our colleagues L. Kenner, M. Susani and M. Schlederer from the Medical University of Vienna and the Ludwig Boltzmann Institute for Cancer Research in Austria, also used tissue samples taken from tumour patients before and after hormone therapy and from patients who no longer respond to this treatment. In all cases, we were able to show that SOCS-1 was present.”
To further develop an understanding of the relationships between SOCS-1 and the cancer cells’ inflammation-related signalling pathways, Prof. Culig selected a sophisticated experiment. Prostate cancer cell lines were treated with IL-6, an interleukin that plays a key role in inflammation. Interestingly, although this did not increase the level of mRNA, which is required to produce SOCS-1, the concentrations of SOCS-1 rose significantly. As Prof. Culig explains, “Although this result is rather surprising at first glance, the explanation may be very simple. It is entirely conceivable that IL-6 has a stabilising effect on the mRNA and that SOCS-1 can thus be produced over a longer period. This also leads to a higher concentration in the cells.”
Given that the effects of the previously identified SOCS proteins in the various types of cancer are very different, Prof. Culig analysed them more closely for SOCS-1 in prostate cancer cells. He selected two further highly informative experiments, one in which the concentration of SOCS-1 in the cells was increased and one in which it was decreased. This made it possible to demonstrate that SOCS-1 inhibits tumour growth by suppressing the proliferation of tumour cells. In particular, it was shown that SOCS-1 has an impact on the synthesis of the cyclin and CDK proteins, both of which help initiate proliferation.
Taken as a whole, this work, that has now also been published as a “featured article” in the American Journal of Pathology, indicates that more attention should be paid to the links with inflammation-related processes when carrying out research into prostate cancer. As the project supported by the FWF suggests, signalling pathways that are responsible for inflammation could influence the progression of tumour growth in prostate cancer.
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Original publication: Suppressor of Cytokine Signalling (SOCS)-1 is Expressed in Human Prostate Cancer and Exerts Growth-inhibitory Function through Down-regulation of Cyclins and Cyclin-dependent Kinases. H. Neuwirt, M. Puhr, F. R. Santer, M. Susani, W. Doppler, G. Marcias, V. Rauch, M. Brugger, A. Hobisch, L. Kenner and Z. Culig. Am. J. Path., DOI 10.2353/ajpath 2009.080751
Prof. Zoran Culig
Innsbruck Medical University
Department of Urology
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Austrian Science Fund FWF:
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Vienna, 27th April 2009