The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice

Abstract

An expression cassette carrying 426 basepairs of the rat probasin (PB) gene promoter and 28 basepairs of 5'-untranslated region is sufficient to target the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene specifically to the prostate in transgenic mice. The PB-CAT transgene was expressed in three of five (60%) independent lines of mice, and this expression, as reported previously for the endogenous rat gene, was male specific, restricted primarily to the lateral, dorsal, and ventral lobes of the prostate, with only very low levels of CAT activity detected in the anterior prostate and seminal vesicles. The developmental and hormonal regulation of the transgene also paralleled that reported for the rat gene, with a 70-fold increase in CAT activity in the mouse prostate observed between 2-7 weeks of age, a time corresponding to sexual maturation. PB-CAT activity in the prostate declined after castration to 3.5% of the precastration level, and the CAT activity in castrated males approached precastration levels when mice were supplemented with testosterone. Transgene expression in castrated males was not induced by dexamethasone. Coinjection of PB-CAT with a chicken lysozyme gene matrix attachment region resulted in their cointegration and further restricted the pattern of PB-CAT to the dorsolateral prostate, with suppressed expression observed in the ventral prostate. These studies demonstrate that a minimal rat probasin promoter can target heterologous gene expression specifically to the prostate in a developmentally and hormonally regulated fashion.

Early and delayed castrations confer a similar survival advantage in TRAMP mice

“…Heterozygous 8-weekold TRAMP mice (C57BL/6-Tg[TRAMP]8247Ng/J), which were purchased from The Jackson Laboratory (Bar Harbor, Maine, USA), were mated with wild-type C57BL/6 mice (Vital river, Beijing, China) to generate both wild-type and heterozygous mice. The progeny was genotyped by PCR as described earlier [10,17], and the male mice that expressed the transgene were randomly divided into three groups. All mice were maintained under specific pathogen-free (SPF) conditions, allowed free access to drinking water and regular meals and kept under a controlled 12-h light/dark cycle at 22 ± 2°C.…”

Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models

“…12,13 Such therapies can be further refined by the use of prostate-specific promoters to drive gene expression. 7,[14][15][16][17][18][19] For systemic therapy, replication competent adenoviruses that are controlled by a tissue-specific promoter are under development. 20 Alternatively, tumor targeting can be achieved by altering the normal tropism of adenovirus infection.…”

Conditional activation of FGFR1 in the prostate epithelium induces angiogenesis with concomitant differential regulation of Ang-1 and Ang-2

“…These mice will exhibit FGFR1-dependent progressive hyperplasia and PIN . Unfortunately, the probasin promoter only becomes active at sexual maturity, typically around 4 weeks of age (Greenberg et al, 1994). Hence, the caFGFR1 model is not ideal for studying the regulation of FGFR1 activity as a function of time.…”