Cel A number of mammalian TRP (Transient Receptor Potential) channel family members show a unique mode of gating in response to thermal stimuli and chemical analogues of heating and cooling sensations capsaicin and menthol, respectively. Out of them the cold/menthol-sensitive TRPM8 seems to be one of the most intriguing while still remaining the least studied. The intrigue comes from the fact that aside from sensory neurons, in which the role of TRPM8 in mediating cold-evoked excitation is fairly well established, it is most abundantly expressed in the prostate - the tissue, which is not involved in temperature-dependent functions. Moreover, whilst remaining at moderate levels in normal prostate, TRPM8 expression strongly increases in prostate cancer. All this suggests that aside from cold sensing demonstrated so far for sensory neurons, TRPM8 may likely have other important functions as well as modes of activation, especially in the prostate, and during carcinogenesis. Thus, the major goal of this project is to establish prostate-specific physiological and pathological roles of TRPM8 and to discover alternative to cold mechanisms of its activation. In the framework of this major goal we will ask the following key questions: 1. What is subcellular localization and functional properties of TRPM8 in prostate epithelial cells and how do they correspond to those of heterologously expressed TRPM8 2. What exogenous and endogenous factor(s) other than cold and menthol may play role in TRPM8 activation/modulation, what mechanisms or signalling pathway(s) are involved in their action and is there any specificity in that respect to prostate cells and sensory neurons? 3. What are the roles of short TRPM8 splice variants in the primary isoform expression, targeting and functional responses in the prostate? 4. How is TRPM8 involved in prostate cancer epithelial cells proliferation differentiation and apoptosis? 5. What is general androgen-dependence of TRPM8 expression and function, and what changes they undergo during malignant transformation of prostate cancer epithelial cells to apoptotic resistant phenotypes characteristic for the late, incurable androgen-independent stage of cancer? Answering these questions will help to understand cell type-specific distribution, functions, and regulation of TRPM8, its roles in normal prostate and during malignant transformation, as well as to establish it as potential therapeutic target in prostate cancer treatment. The research will require multidisciplinary approach (electrophysiology, imaging, molecular biology and immunology) involving multiple cell preparations (cell lines, native prostate epithelial cells of different origin, dorsal root ganglion neurons). Słowa kluczowe Biophysics Molecular Neuroscience Signal Transduction Program(-y) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Temat(-y) Data not available Zaproszenie do składania wniosków Data not available System finansowania Data not available Koordynator UNIVERSITÉ DES SCIENCES ET TECHNOLOGIES DE LILLE & INSERM Wkład UE Brak danych Adres CITÉ SCIENTIFIQUE, SN3 VILLENEUVE D'ASCQ Francja Zobacz na mapie Koszt całkowity Brak danych Uczestnicy (3) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko A.A. BOGOMOLETZ INSTITUTE OF PHYSIOLOGY Ukraina Wkład UE Brak danych Adres BOGOMOLETZ STREET, 4 KYIV Zobacz na mapie Koszt całkowity Brak danych INTERNATIONAL CENTER FOR MOLECULAR PHYSIOLOGY Ukraina Wkład UE Brak danych Adres BOGOMOLETZ STREET, 4 KYIV Zobacz na mapie Koszt całkowity Brak danych UNIVERSITÄT LINZ Austria Wkład UE Brak danych Adres ALTENBERGERSTRASSE, 69 LINZ Zobacz na mapie Koszt całkowity Brak danych
