BMC Cancer 1BR2M0e0Cs1eC,aanrccerh article :19 BioMed Central IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells Beverly E Barton*1, Thomas F Murphy1, Patricia Adem1, Richard A Watson2, Robert J Irwin2 and Hosea F Huang2,3 Address: 1Division of General Surgery, Department of Surgery, UMDNJ-NJMS, 185 S. Orange Ave., Newark, NJ 07103, USA, 2Division of Urology, Department of Surgery, UMDNJ-NJMS, 185 S. Orange Ave., Newark, NJ 07103, USA and 3Department of Veterans' Affairs, New Jersey, Health Care System at East Orange, NJ OJ 019, USA E-mail: Beverly E Barton* - bartonbe@umdnj.edu; Thomas F Murphy - Murphytf@umdnj.edu; Patricia Adem - Adempa@umedj.edu; Richard A Watson - Watsonra@umdnj.edu; Robert J Irwin - Irwinrj@umdnj.edu; Hosea F Huang - huanghf@umdnj.edu *Corresponding author Published: 31 October 2001 BMC Cancer 2001, 1:19 Received: 16 July 2001 Accepted: 31 October 2001 This article is available from: http://www.biomedcentral.com/1471-2407/1/19 © 2001 Barton et al; licensee BioMed Central Ltd. Verbatim copying and redistribution of this article are permitted in any medium for any non-com- mercial purpose, provided this notice is preserved along with the article's original URL. For commercial use, contact info@biomedcentral.com Abstract Background: STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic. Methods: We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells. Results: Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells. Conclusions: We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed. Background Prostate cancer (PCA) is the leading cause of death in the American male over age 55, according to recent data [1]. To date, the mechanisms underlying the pathogenesis of this disease, including how normal prostate cells become neoplastic, remain unidentified. Moreover, the treat- ment efficacy of this disease remains limited, especially when it recurs. A thorough understanding of the neo- plastic process could facilitate earlier detection of the disease, lead to more specific therapies for PCA, and ul- timately improve survival. PCA is one of several types of cancers in which IL-6 has been found or is thought to play a pathophysiological role. Some researchers think IL-6 may play a role in PCA because of what IL-6 does in other model systems of can-