Disease relevance of SMR3B

• Our findings provide direct evidence that PRL-3 may be involved in triggering angiogenesis and establishing microvasculature and it may serve as an attractive therapeutic target with respect to both angiogenesis and cancer metastasis [1].
• Because PRL-3 mRNA had been reported to be consistently elevated in metastatic samples derived from colorectal cancers, we attempted to investigate if PRL-3 might be involved in tumor angiogenesis and if PRL-3-expressing cells could cross-talk to human umbilical vascular endothelial cells (HUVEC) by using an in vitro coculture system [1].
• We observed that both PRL-3-expressing Chinese hamster ovary (CHO) cells and PRL-3-expressing DLD-1 human colon cancer cells could redirect the migration of HUVECs toward them; in addition, PRL-3-expressing DLD-1 cells could enhance HUVEC vascular formation [1].
• Subsequent analysis indicated that the expression of HAI-2/PB suppressed the fibrinolytic activities of both glioblastoma cell lines [2].
• However, the correlation between the PRL-3 expression and clinical outcome in breast cancer has not been investigated [3].

High impact information on SMR3B

• PRL-3 Initiates Tumor Angiogenesis by Recruiting Endothelial Cells In vitro and In vivo [1].
• In vivo injection of PRL-3-expressing CHO cells into nude mice to form local tumors resulted in the recruitment of host endothelial cells into the tumors and initiation of angiogenesis [1].
• We show here that PRL-3 protein is expressed in fetal heart, developing blood vessels, and pre-erythrocytes but not in their mature counterparts [1].
• HUVECs were grown with fibroblasts, which were later overlaid with PRL-3-expressing cells [1].
• Neither PSA, PB, nor ARR3 androgen-responsive reporters could be induced by activation of PKA in the absence of transfected AR [4].

Chemical compound and disease context of SMR3B

• Previous microarray analysis demonstrated that 14 genes, including hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI2/PB) gene, showed particularly high inductions after 5-aza-2'deoxycytidine (5Aza-dC) treatment in multiple hepatoma cell lines [5].
• The association of the expression level of protein tyrosine phosphatase PRL-3 protein with liver metastasis and prognosis of patients with colorectal cancer [6].
• Therefore it is of interest to investigate whether expression of human c-Ha-ras affects the androgen-dependence of prostate carcinomas developing in the PB/SV40T Tg rat [7].

Biological context of SMR3B

• Nucleotide sequence of gene PBII encoding salivary proline-rich protein P-B [8].
• PBII is 7.1 kb long and contains 3 exons [8].
• The Pbx binding site in the PRL3 nGRE, located just upstream of the Oct-1 binding site, showed a strong sequence similarity with known Pbx binding sites and bound Pbx with an affinity similar to that of other established Pbx target sequences [9].
• The GST-WPBF expressed in bacteria binds the Prolamin box (PB) 5'-TGTAAAG-3', derived from the promoter region of a native alpha-gliadin gene encoding a storage protein [10].
• BACKGROUND: Increasing evidence has suggested that phosphatase of regenerating liver-3 (PRL-3) plays an important role in cancer cell migration, invasion and metastasis [3].

Anatomical context of SMR3B

• Further investigations will be necessary to establish the origin of statherin and PB salivary peptide in gingival crevicular fluid [11].
• Transient expression experiments in co-transfected BY-2 protoplast cells demonstrated that WPBF trans-activated transcription from native alpha-gliadin promoter through binding to the intact PB [10].
• High expression of PRL-3, a protein tyrosine phosphatase, is proved to be associated with lymph node metastasis in gastric carcinoma from previous studies [12].
• METHODS: MAb against PRL-3 was prepared with the hybridoma technique, and its specificity was confirmed with ELISA and Western blotting assays [6].
• This part of the sequence is identical to the corresponding region of human P-B cDNA from the submaxillary gland [13].

Associations of SMR3B with chemical compounds

• Using the SDS-PAGE assay, we found that, in contrast to previous reports, the tyrosine phosphatase PRL-3 may possibly be a dual substrate for both FTase and GGTase-I [14].
• To determine whether smoking affects androgen and estrogen production and metabolism we measured the MCRs, production rates (PB), androgen and estrogen interconversions, and percent peripheral aromatization in 88 pre- and postmenopausal women grouped as smokers or nonsmokers [15].
• This anti-invasive effect appeared to be mediated primarily by the inhibitory activity of HAI-2/PB against the serine proteinase-dependent matrix degradation [2].
• Furthermore, the addition of 4% polyethylene glycol (PEG) gave a better resolution of 4 peaks, resulting in the separation of the overlapped peaks of PB and AB [16].
• Two biflavonoids, ginkgetin (1) and sciadopitysin (2), were isolated from the MeOH extract of the young branches of Taxus cuspidata, which inhibited phosphatase of regenerating liver-3 (PRL-3) with IC(50) values of 25.8 and 46.2 muM, respectively [17].

Other interactions of SMR3B

• Detection in human saliva of different statherin and P-B fragments and derivatives [18].
• Salivary P-B peptide is usually included into the basic proline-rich protein family but it shows some similarities with statherin and its specific biological role is still undefined [18].

Analytical, diagnostic and therapeutic context of SMR3B

• Molecular cloning and sequence analysis of cDNA coding for the precursor of the human salivary proline-rich peptide P-B [19].
• PATIENTS AND METHODS: Using a PRL-3-specific monoclonal antibody 3B6, PRL-3 expression was assessed by immunohistochemistry in tumor tissues from 382 breast cancer patients with a median follow-up of 65 months [3].
• Sequence analysis identified 18 peptides that appear to be proteolytic cleavage products of the basic proline-rich proteins IB-4, IB-5, IB-7, IB-8b, and P-B [20].
• METHODS: The levels of PRL-3 mRNA expression in 8 gastric cancer cell lines were examined by RT-PCR [21].

References