Disease relevance of Pbsn

• Isolation and characterization of mouse probasin will facilitate further development and analysis of autochthonous mouse models of prostate cancer [1].
• Probasin protein and RNA expression were examined by immunobloting, immunohistochemistry, and RT-PCR, in normal mouse prostate tissue and tumor tissues derived from the autochthonous "transgenic adenocarcinoma of the mouse prostate" (TRAMP) model [1].
• METHODS: Mouse probasin cDNA was isolated from a phage library, and the DNA sequence was determined [1].
• Hence, in the 12T-10 large probasin promoter-Tag mouse, high-grade prostatic intraepithelial neoplasia develops progressively greater NE differentiation and progresses to invasive adenocarcinoma and NE carcinoma, with a high percentage of metastases [2].
• A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential [2].

High impact information on Pbsn

• Use of the probasin promoter ARR2PB to express Bax in androgen receptor-positive prostate cancer cells [3].
• Therefore, we developed an adenoviral construct (Av-ARR2PB-Bax) in which the probasin promoter, modified to contain two androgen response elements, drives Bax expression [3].
• However, association was not detected with mutant receptors inactivated by an internal deletion or a point mutation, Trp282 to Arg, in a membrane-proximal cytoplasmic region (PB or PM4 mutant, respectively) [4].
• A luciferase reporter gene was directed to the prostate epithelium using three composite promoters called human kallikrein 2 (hK2)-E3/P, PSA-E2/P, and ARR2PB, derived from hK2, PSA, and rat probasin regulatory elements, to generate the EZC1, EZC2, and EZC3-prostate mice, respectively [5].
• We generated four independent lines of transgenic mice with targeted overexpression of FGF8b in the prostatic epithelium using an improved rat probasin promoter, ARR(2)PB [6].

Chemical compound and disease context of Pbsn

• We demonstrate that in G0, AR enhances transcription from an integrated steroid-responsive mouse mammary tumor virus promoter and also from an integrated androgen-specific probasin promoter [7].
• In this investigation we present data generated with adenovirus AvARR(2)PB-Bad, in which the apoptotic gene bad was placed under the control of the dihydrotestosterone (DHT)-inducible third-generation probasin-derived promoter ARR(2)PB [8].
• In castrated animals, a single, low, environmentally relevant dose of cadmium (20 microg/kg body weight) increased the wet weight of the prostate (1.97- to 3-fold) and the seminal vesicle complex (approximately 1.5-fold) and increased the expression of the androgen-regulated gene, probasin (27-fold) [9].
• In a burn model the effect of a subtherapeutic dose of polymyxin B-sulfate (PB) at BT was examined in Escherichia coli-monoassociated mice with Pseudomonas aeruginosa-inoculated burn wounds [10].

Biological context of Pbsn

• Furthermore, DFMO treatment resulted in the marked reduction in the protein expression of proliferation cell nuclear antigen, ODC, and probasin in the dorsolateral prostate [11].
• We used the probasin promoter to target a human bcl-2 transgene specifically to the prostate in order to assess its impact on conferring resistance to androgen withdrawal in, otherwise sensitive, prostatic glandular epithelial cells in vivo [12].
• There was no difference between probasin bcl-2 transgenic mice, bax-/- mice, and control littermates in steady-state levels of apoptosis [12].
• A small composite probasin promoter confers high levels of prostate-specific gene expression through regulation by androgens and glucocorticoids in vitro and in vivo [13].
• The hyperplastic prostates of Pb-PRL transgenic mice demonstrate a molecular pattern supporting the importance of reduced degree of apoptosis for the development of the phenotype [14].

Anatomical context of Pbsn

• The expression of probasin was primarily localized to the apical membrane of differentiated secretory epithelium [1].
• Consistent with this finding, we observed that the SV40 Tag and endogenous mouse probasin genes are expressed at low levels in the thymus [15].
• A second-generation adenoviral vector was constructed with the modified prostate-specific probasin promoter, ARR2PB, directing expression of an HA-tagged Bax gene and a green fluorescent protein reporter translated from an internal ribosome entry site (ARR2PB.Bax.GFP) [16].
• Thus, a composite probasin promoter (ARR2PB) coupled to the bacterial chloramphenicol acetyltransferase reporter (ARR2PBCAT) was generated and tested in prostatic and nonprostatic cell lines and in a transgenic mouse model [13].
• (3) PB-activated macrophages are more sensitive to TrB blockage [17].

Associations of Pbsn with chemical compounds

• Probasin is a prostate-specific gene originally isolated from the rat and has been exploited as a marker of prostate differentiation and to elucidate androgen action [1].
• The addition of low doses of the cationic polypeptide antibiotic, polymyxin B (PB), to cultures of mouse spleen cells inhibits lipopolysaccharide-(LPS) induced DNA synthesis but not that stimulated by PPD, PHA, or Con A [18].
• Selective activation of the probasin androgen-responsive region by steroid hormones [19].
• Surprisingly, PB also reduced proliferation to detoxified LPS [20].
• The tumor-suppressive effect of PB disappeared after macrophage system blockage with TrB [17].

Regulatory relationships of Pbsn

• The transgenic adenocarcinoma of mouse prostate (TRAMP) model is transgenic for the SV40 large T Ag (Tag) under the control of the rat probasin regulatory elements [15].
• In conclusion, IGF-I transgenic mice under the control of rat probasin promoter showed more dense and enlarged epithelial glands in their prostatic ventral, dorsal and lateral lobes [21].
• Additionally, we have established mouse dermatopontin transgenic mice under the control of the rat probasin promoter [22].

Other interactions of Pbsn

• Isolation and characterization of mouse probasin: An androgen-regulated protein specifically expressed in the differentiated prostate [1].
• Prostatic intraepithelial neoplasia and adenocarcinoma in mice expressing a probasin-Neu oncogenic transgene [23].
• Instead, immunohistochemistry of the prostate-specific secretory marker, probasin, suggested that hypersecretory function of the epithelium could underlie local congestion and cyst formation in prostates of Stat5a-null mice [24].
• Seven lines of transgenic mice with the rat prostate-specific large probasin promoter linked to the SV40-large T antigen (Tag) that develop prostatic neoplasia have been established [2].
• TCDD reduced dorsolateral prostate weight in wild-type but not AhRKO mice and had no significant effect on expression of mRNA for PSP94 or for probasin, a major androgen-dependent secretory protein [25].

Analytical, diagnostic and therapeutic context of Pbsn

• Regulation of probasin expression in response to surgical castration and hormone supplementation was also characterized [1].
• To develop an animal model for prostate cancer, several lines of transgenic mice were generated by using the prostate-specific rat probasin promoter to derive expression of the simian virus 40 large tumor antigen-coding region [26].
• The objective of this study was to characterize the molecular mechanisms involved in the prostate hyperplasia seen in the Pb-PRL transgenic mice. cDNA microarray analysis was used to identify differentially expressed transcripts in the hyperplastic prostates of 6-month-old transgenic mice compared with age-matched controls [14].
• Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls [27].
• An allograft model of androgen independent prostatic neuroendocrine carcinoma derived from a large probasin promoter-T antigen transgenic mouse line [28].

References