Prostate Cancer Basic Research Session II - AUA 2006

UroToday.com - A Discussed Poster Session on Prostate Cancer Basic Research took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. A few of the many interesting posters on basic and potential translation science are described herein.

Dr. Davis Syme, Melbourne, Australia reported the effect of castration on cavernous nerve graft regeneration. Rats underwent bilateral cavernous nerve neurotomy followed by unilateral interpositional nerve graft using the genitofemoral nerve. Animals were then randomized to undergo castration, remain hormonally intact or receive testosterone. Electrostimulation of the nerve grafts was performed at 3 months and histologic analysis performed. Castration resulted in a significant reduction to electrostimulation and clinical application suggests that nerve grafts would be of little use in patients who may need androgen deprivation following surgery.

Dr. Christopher Evans, UC Davis presented work in a chimeric animal tumor model. His laboratory demonstrated that neuropeptide overexpressing androgen-insensitive CaP cells supported the growth and migration of androgen-sensitive CaP cells in androgen-deprived in vitro and in vivo environments. They have also shown that CaP cells express neuropeptides at the time of androgen-withdrawal. Taken together, this suggests that at the time of castration, some androgen-sensitive CaP cells may escape cell death due to paracrine support from surrounding neuropeptide expressing CaP cells.

Dr. Deka from Northwestern University reported that variants in the HEPSIN gene are associated with CaP in Caucasian men. The HEPSIN gene is located on chromosome 9q and codes for a transmembrane cell surface serine protease that is over-expressed in CaP. A comparison was made between 604 men with CaP and 576 controls, all Caucasian. Five of 11 single nucleotide polymorphisms on the HEPSIN gene were found to have significant differences in allele frequencies between the groups. This suggests an association between genetic variants in HEPSIN and CaP carcinogenesis in Caucasian men.

Dr. Wu from the laboratory of Dr. Dan Theodorescu, University of Virginia reported on the tumor suppressor gene PTEN and its effect on CaP cell migration in the bone microenvironment. PTEN was expressed in a PTEN-null CaP cell line, C4-2. The PTEN cells selectively migrated towards proteins expressed by bone calavaria compared to proteins expressed by lung fibroblast cells. Compared to control cells, the PTEN cells did not show increased proliferation, suggesting that the effect is purely on migration and not due to enhanced growth. Further experiments identified the PTEN mechanism as mediated through the small GTPase Rac1.

By Christopher P. Evans, M.D.

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