SOCS in human prostate cancer

Interleukin-6 (IL-6) is a cytokine that is involved in the regulation of cell growth, survival, and immune responses in prostate cancer. IL-6 causes multifunctional responses in carcinoma of the prostate ranging from inhibition of tumour cell growth to enhancement of survival. IL-6 levels are elevated in tissues and sera of prostate cancer patients and new therapy concepts with aim to interfere with IL-6 action could be established. These novel therapy approaches can be proposed if IL-6 signalling in prostate cancer is better understood. IL-6 effects in malignancies greatly depend on endogenous suppressors of cytokine signalling (SOCS) whose role in carcinoma of the prostate has not been investigated yet. In the present project, we propose to investigate expression of SOCS in prostate cancer cell lines. Prostate cancer cells with low expression of SOCS will be then treated with IL-6 or related cytokines to induce expression of SOCS. In some other organ systems, induction of SOCS leads to efficient attenuation of cytokine signalling, a fact that might be of potential importance for anti-IL-6-based therapies. It will also be investigated whether hypermethylation of promoters of SOCS genes is responsible for silencing their expression in prostate cancer. Well also study consequences of association between SOCS and receptors tyrosine kinase that may lead to inactivation of these receptors which are overexpressed at least in a subgroup of prostate cancer patients. Finally, SOCS cDNA will be overexpressed in prostate cancer cells and the consequences of this transfection on regulation of cyclin-dependent kinases, cyclins and tumour suppressors will be investigated. Prostate cancer cell lines stably transfected with SOCS will be then used in animal experiments and tumour volume will be measured and compared to that determined in animals inoculated with cells transfected with an empty vector.

Interleukin-6 (IL-6) is a cytokine that is involved in the regulation of cell growth, survival, and immune responses in prostate cancer. IL-6 causes multifunctional responses in carcinoma of the prostate ranging from inhibition of tumour cell growth to enhancement of survival. IL-6 levels are elevated in tissues and sera of prostate cancer patients and new therapy concepts with aim to interfere with IL-6 action could be established. These novel therapy approaches can be proposed if IL-6 signalling in prostate cancer is better understood. IL-6 effects in malignancies greatly depend on endogenous suppressors of cytokine signalling (SOCS) whose role in carcinoma of the prostate has not been investigated yet. In the present project, we propose to investigate expression of SOCS in prostate cancer cell lines. Prostate cancer cells with low expression of SOCS will be then treated with IL-6 or related cytokines to induce expression of SOCS. In some other organ systems, induction of SOCS leads to efficient attenuation of cytokine signalling, a fact that might be of potential importance for anti-IL-6-based therapies. It will also be investigated whether hypermethylation of promoters of SOCS genes is responsible for silencing their expression in prostate cancer. We`ll also study consequences of association between SOCS and receptors tyrosine kinase that may lead to inactivation of these receptors which are overexpressed at least in a subgroup of prostate cancer patients. Finally, SOCS cDNA will be overexpressed in prostate cancer cells and the consequences of this transfection on regulation of cyclin-dependent kinases, cyclins and tumour suppressors will be investigated. Prostate cancer cell lines stably transfected with SOCS will be then used in animal experiments and tumour volume will be measured and compared to that determined in animals inoculated with cells transfected with an empty vector.