Disease relevance of Msmb

• To explore its utility for prostate targeting, we have studied the gene expression of PSP94 with rat probasin (rPB), a gene commonly used for prostate targeting in prostate cancer research and a gene typically responsive to androgen regulation [1].
• Prostate secretory protein PSP-94 decreases tumor growth and hypercalcemia of malignancy in a syngenic in vivo model of prostate cancer [2].
• In the adenocarcinoma, signals of probasin but not PSP94 and SVSII were detected [3].
• A daily injection of PSP94 at 5 microg/kg/body weight resulted in a 50-60% inhibition in the growth of PC3 xenografts in athymic mice [4].
• Interestingly, equimolar concentrations of PCK3145 were shown to be more effective in delaying the development of experimental skeletal metastases as compared to PSP-94 [5].

High impact information on Msmb

• In previous studies, we have shown that prostate secretory protein (PSP-94) can reduce prostate cancer growth in vivo [6].
• In the current study, we identified the amino acid sequence of PSP-94 that is required for eliciting this response [6].
• Whereas the highest dose of PSP-94 caused a modest but statistically significant delay in the development of hind-limb paralysis, a marked dose-dependent decrease in primary tumor volume was seen in experimental animals receiving PSP-94 due to its ability to promote tumor cell apoptosis [2].
• Secondly, we found that PSP94 gene transcription decreased relatively slowly in response to androgen deprivation but recovered rapidly in response to testosterone replacement after complete ablation of PSP94 transcription [1].
• Rodent PSP94 gene expression is more specific to the dorsolateral prostate and less sensitive to androgen ablation than probasin [1].

Biological context of Msmb

• We conclude that PSP94 gene expression at the transcriptional level is more specific to the LP and DP than rPB and thus less sensitive to androgen ablation [1].
• PC3 cell growth inhibition by PSP94 resulted from cell death characteristic of morphological apoptosis, which was confirmed by dual fluorescence microscopy, electron microscopy, and DNA fragmentation assays [4].

Anatomical context of Msmb

• beta-Microseminoprotein is a small, nonglycosylated protein, rich in disulfide bonds, which is present in the secretions of the airways, the gastrointestinal tract, and the urogenital tract [7].
• Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis [4].
• Beta-microseminoprotein (beta-MSP), a sperm-coating antigen isolated from human seminal plasma, has apparent structural identity with "beta-inhibin" isolated from the same source [8].
• BACKGROUND: Prostatic secretory protein of 94 amino acids (PSP94), probasin, and seminal vesicle secretion II (SVSII) are the three major proteins secreted by the lateral lobe of the rat prostate gland [3].

Associations of Msmb with chemical compounds

• Thirdly, Western blot analysis revealed that both PSP94 and rPB expression is specific to the LP and DP at the protein level, exhibiting slow responses to testosterone replacement after castration [1].
• We observed that the mRNA transcripts of both PSP94 and probasin were increased after treatments with DHT, DEX, and MPA, suggesting that these two proteins could also be regulated by glucocorticoid and progestin [9].
• BACKGROUND: Prostatic secretory protein of 94 amino acids (PSP94), also called beta-microseminoprotein, is a small, nonglycosylated protein, rich in cysteine residues [10].

Analytical, diagnostic and therapeutic context of Msmb

• Time of hind-limb paralysis and tumor volume were determined, and comparison was made between PSP-94-treated animals and control animals receiving vehicle alone [2].
• Furthermore, whereas control animals routinely developed hypercalcemia due to PTHrP production, treatment with PSP-94 led to a near normalization of plasma calcium and a marked reduction in PTHrP production as determined by radioimmunoassay and immunohistochemistry [2].
• The results of in situ hybridization showed that PSP94, probasin, and SVSII were highly expressed in the intact LP [9].
• Their mRNA levels dropped in response to duration of castration in the following decreasing order: SVSII, PSP94, and probasin [9].
• Immunohistochemistry of PSP94 also showed a reduced staining in the PIN lesions, but no immunoreactivity was seen in the rat prostatic tumors [3].

References