These effects are clearly different from those manifested upon activation of the intracellular androgen receptors mediating genomic androgen our website signals resulting in receptor dimerization, nuclear translocation and subse quent activation of androgen specific target genes. The mAR dependent signaling Inhibitors,Modulators,Libraries was recently characterized in detail in prostate and breast cancer cell lines. Using non permeable androgen derivatives that do not bind to iAR, it was shown that mAR activation resulted in actin reorganization regulated by mechanisms involving small GTPases. Furthermore, it was shown that mAR activation induced profound apoptotic regression of prostate cancer cells in vitro and in mouse xenografts in vivo and suppressed cell growth and motility.

Finally, most recent studies have impli cated key pro survival and pro apoptotic gene products such as AKT, NFB, Bad, Fas and caspase 3 in the regula tion of the apoptotic response induced by mAR activation in prostate cancer cells. Inhibitors,Modulators,Libraries Taken together, these studies clearly established that func tional mARs trigger strong anti tumorigenic effects, imply ing a potential role of mAR as a novel target for the development of selective cancer treatments. However, it remained elusive whether mARs are also expressed in other tumors and whether their activa tion could result in the induction of anti tumorigenic effects similar to the ones described in prostate and breast cancer cells. Colon tissues are known to express functional nuclear hormone receptors, and spe cific AR, ER and ER genotypes have been associated with colon cancer.

Moreover, administration of androgens has been linked Inhibitors,Modulators,Libraries to the promotion of colon can cer tumorigenesis in rats. Inhibitors,Modulators,Libraries On the other hand, steroid hormones induced tumor growth remission in xenotrans planted adenocarcinomas in nude mice, arguing for a more complex role of steroid hormones in colon cancer. Since the membrane androgen receptor, in contrast to the classical intracellular androgen receptor, induces tumor regression in target tissues, we sought to determine the expression and functional status of mAR in colon cancer. To this end, we used colon cancer tissues isolated from mice xenograft tumors and from two estab lished colon cancer cell lines. As a result, testosterone binding sites were expressed in the membrane of colon cancer cells and qualify as bona fide membrane androgen Inhibitors,Modulators,Libraries receptors as assessed by radioli gand binding studies, Scatchard analysis and displace ment assays.

The activation of those receptors with non permeable testosterone derivatives triggered rapid and profound actin and tubulin cytoskeleton reorganization and induced pro apoptotic responses. Finally, treatment of Balb c mice with testosterone albumin conjugates resulted in considerable anti tumor activity selleck chem Tubacin in vivo.