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Transgenic (TG) rats bearing a probasin promoter/simian virus 40 T antigen (SV40 Tag) construct were treated with antiandrogens to examine their ability to suppress prostate carcinogenesis. Finasteride and flutamide were administered to 10-week-old TG rats five times a week for 2, 5 and 7 weeks. Antiandrogen-treated prostates exhibited atrophic glandular structures with almost no expression of SV40 Tag and only weak signals for androgen receptors. Furthermore, quantitative data for ventral prostate adenocarcinomas showed significant decrease with antiandrogen treatment. Both finasteride and flutamide had the ability to suppress SV40 Tag-driven carcinogenesis through their different antiandrogenic mechanisms, suggesting that this TG model is suitable for exploring the potential of agents to inhibit prostate cancer development.Prostate Cancer and Prostatic Diseases (2007) 10, 378–383; doi:10.1038/sj.pcan.4500971; published online 24 April 2007 [ABSTRACT FROM AUTHOR]

There is a large body of evidence suggesting the connexin gap junction proteins appear to act as tumor suppressors, and their tumor inhibitory effect is usually attributed to their main function of cell coupling through gap junctions. However, some cancer cells (e.g. the rat bladder carcinoma BC31 cell line) are cell–cell communication proficient. Using specific site-directed mutagenesis in the third membrane-spanning (3M) domain of connexin43 (Cx43), we abolished the intrinsic gap junction intercellular communication (GJIC) in BC31 cells either by closing the gap junctional channels or by disruption of the transport of connexin complexes to the lateral membrane. Clones of BC31 cells transfected with a dominant negative Cx43 mutant giving rise to gap junctional channels, permeable only for a small tracer (neurobiotin), displayed accelerated growth rate in vivo, showing the critical role of selective gap junctional permeability in the regulation of cell growth in vivo. The use of other dominant-negative mutants of Cx43 also suggested that the effect of impaired communication on the tumorigenicity of cancer cells depends on the subcellular location of connexin. Inhibition of intrinsic GJIC in BC31 cells by sequestering of Cx protein inside the cytoplasm, due to expression of dominant-negative transport-deficient Cx43 mutants, did not significantly enhance the growth of transfectants in nude mice, but occasionally slightly retarded it. In contrast, augmentation of GJIC in BC31 cells by forced expression of wild-type Cx43, or a communication-silent mutant, fully suppressed tumorigenicity of these cells. Overall, these results show that cell coupling is a strong, but not the sole, mechanism by which Cx suppresses growth of tumorigenic cells in vivo; a GJIC-independent activity of Cx proteins should be considered as another strong tumor-suppressive factor. Oncogene (2000) 19, 505–513. [ABSTRACT FROM AUTHOR]

Expression of epithelial membrane antigen (EMA) was investigated immunohistochemically in 27 cases of bladder carcinoma using a monoclonal antibody. Normal urothelial epithelium showed EMA staining restricted to the upper layer of the surface epithelium. G-I transitional cell carcinomas demonstrated positive EMA staining which could be divided into the following 3 types; type 1, in which highly stained cells occurred in the upper layer of the neoplastic epithelium; type 2, in which the whole tumour focus was slightly stained; and type 3, in which cells strongly positive for EMA were scattered throughout the tumour focus. G-III (undifferentiated) transitional cell lesions exhibited irregular expression of EMA whereas squamous cell demonstrated specific intense EMA staining within keratinized tumour cells. [ABSTRACT FROM AUTHOR]

Expression of involucrin was investigated immunohistochemically in 27 cases of urinary bladder carcinoma. Although no keratinization was observed in the transitional cell carcinomas examined all displayed involucrin staining to various degrees. Involucrin expression in foci of G-I transitional cell carcinomas was classified into 3 types: type 1, a mixture of intensely stained and slightly positive cells; type 2, highly positive cells intermingled with negative tumour cells; and type 3, all tumour cells slightly positive. Undifferentiated cell carcinomas demonstrated an irregular distribution of involucrin of varying staining intensity while deposition in squamous cell carcinomas was limited to keratinized areas. [ABSTRACT FROM AUTHOR]