%0 Journal Article
%T Stable expression of constitutively-activated STAT3 in benign prostatic epithelial cells changes their phenotype to that resembling malignant cells
%A Hosea F Huang
%A Thomas F Murphy
%A Ping Shu
%A Arnold B Barton
%A Beverly E Barton
%J Molecular Cancer
%D 2005
%I BioMed Central
%R 10.1186/1476-4598-4-2
%X We observed that prostatic cell lines stably expressing S3c required STAT3 expression for survival, because they became sensitive to antisense oligonucleotide for STAT3. However, S3c-transfected cells were not sensitive to the effects of JAK inhibitors, meaning that STAT3 was constitutively-activated in these transfected cell lines. NRP-152 prostatic epithelial cells lost the requirement for exogenous growth factors. Furthermore, we observed that NRP-152 expressing S3c had enhanced mRNA levels of retinoic acid receptor (RAR)-¦Á, reduced mRNA levels of RAR-¦Â and -¦Ã, while BPH-1 cells transfected with S3c became insensitive to the effects of androgen, and also to the effects of a testosterone antagonist. Both S3c-transfected cell lines grew in soft agar after stable transfection with S3c, however neither S3c-transfected cell line was tumorigenic in severe-combined immunodeficient mice.We conclude, based on our findings, that persistently-activated STAT3 is an important molecular marker of prostate cancer, which develops in formerly benign prostate cells and changes their phenotype to one more closely resembling transformed prostate cells. That the S3c-transfected cell lines require the continued expression of S3c demonstrates that a significant phenotypic change occurred in the cells. These conclusions are based on our data with respect to loss of growth factor requirement, loss of androgen response, gain of growth in soft agar, and changes in RAR subunit expression, all of which are consistent with a malignant phenotype in prostate cancer. However, an additional genetic change may be required for S3c-transfected prostate cells to become tumorigenic.Signal transducers and activators of gene transcription (STATs) are, as their name suggests, proteins that regulate gene expression by affecting transcription. They are part of the signal transduction pathway used by many growth factors and cytokines, and are activated by phosphorylation of tyrosine and serine residues by u
%U http://www.molecular-cancer.com/content/4/1/2