Understanding the Mechanisms of Modulation of Cellular Growth and Tumorigenesis by Interlukin-6 in Human Prostate and Bladder Carcinoma Cells.

Although the PC incidence differs considerably among the various racial-ethnic groups around world and Chinese have low ratio for PC, recently report from NIH in Taiwan indicated PC is up to the 7th leading cause of cancer-related death in Taiwan. Bladder cancer is the 5th most frequent malignant disease around world-wild. IL-6 regulates many physiological and pathological mechanisms, such as inflammation and immune response, bone metabolism, etc., in the pathologically, IL-6 is discovered in many cancers, like prostate cancer, breast cancer, bladder cancer, kidney cancer and brain tumors. However, the functions of IL-6 in microenvironment of cancer may be quite different from the systemic environment of body. Studies have pointed out that compare with localized prostate cancer, advance prostate cancer patients have higher levels of IL-6 secretion into blood, and cachectic patients higher IL-6 secreted than non-cachectic patients. Several studies have indicated that IL-6 plays an important role for androgen-independent prostate cancer. However, in vitro studies, the divergent effect of L-6 on cell proliferation is dependent on cell types. IL-6 regulates development, proliferation, survival and other gene expression through JAK/STAT3, MAPK and PI3K/Akt pathway. IL-6 also enhances the expression of prostate specific antigen, a prostate tumor marker. On the other hand, our preliminary studies indicated that IL-6 blocked cell proliferation and tumorigenessis of bladder carcinoma cells in vitro and xanograph animal model. Results of the function of IL-6 on prostate or bladder cancer are still contrary and the detailed mechanisms remain unclear. In this proposal using prostate (LNCaP, PCJ, and PC3) and bladder cancer cell line (HT1376 and T24), PI will discuss (1) understand and characterize the function of IL-6 gene in the growth and metastasis of prostate and bladder cancer, (2) understand IL-6 how to regulate it’s target gene expression and the signaling pathway. We will use immunoblotting blot, enzyme immunoassay, transient gene expression assay and animal experiments to approach this goal. The long-term objectives of this thesis are to understand the regulatory mechanisms of IL-6 gene in the neoplasia of the prostate and bladder, and to employ these concepts in the early diagnosis, drug screen, and gene therapy of the disease of prostate and bladder carcinoma.

Project ID:PC10107-0362
External Project ID:NSC101-2314-B182-012-MY3