Disease relevance of TPD52

• PrLZ, a novel prostate-specific and androgen-responsive gene of the TPD52 family, amplified in chromosome 8q21.1 and overexpressed in human prostate cancer [1].
• TPD52 subcellular localization was predominantly cytoplasmic, although nuclear localization was also frequently observed in mucinous and clear cell carcinomas [2].
• Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer [2].
• We have previously reported D53, a member of the tumor protein D52 family, to be a novel 14-3-3 partner protein in breast cancer cells [3].
• Most of the liver metastases showed higher DNA copy number ratios than the corresponding primary tumors, but this difference was only significant for TPD52 (p=0.02) and EIF3S6 (p=0.007) [4].
• On prostate cancer development, PrLZ expression is reactivated, and its expression increases from primary localized tumor to bone metastasis [5].
• The D52 (8q21.13), D54 (20q13.33), and MAL2 (8q24.12) genes were significantly overexpressed in breast cancer tissue (n = 95) relative to normal breast (n = 7; P </= 0.005) unlike the D53 gene (6q22.31; P = 0.884) [6].

Psychiatry related information on TPD52

• The level of risk-taking behaviour in the aquarium study positively correlated with lake-specific PC1 scores [7].
• Finally, an awareness of possible genetic causes of eating disorders will help determine the causes--and thus the treatments--in children and adolescents with eating disorders, as exemplified by obese patients with mutations in the POMC, PC1, leptin, and MC4R loci [8].

High impact information on TPD52

• This 3 bp deletion (AAC) in exon 1 of K6a removes a highly conserved asparagine residue (delta N170) from position 8 of the 1A helical domain (delta N8) [9].
• Antibody to PC-1, another ectoNTPPHase, reacted with 1% SDS extracts of whole chondrocytes but not against those chromatographic fractions containing the major portion of NTPPHase activity [10].
• The present study demonstrates that stable expression of sst2 in the hamster pancreatic cancer cells PC-1 and PC-1.0 activates an autocrine negative loop leading to an in vitro inhibition of cell proliferation [11].
• Human chondrocyte NTPPPH activity was largely attributable to plasma cell membrane glycoprotein 1, PC-1 [12].
• In the Thiel myeloma cell line, TPD52 bound to annexin VI in a Ca(2+)-dependent manner, suggesting that these molecules may act in concert to regulate secretory processes in plasma cells, similarly to what was observed in pancreatic acinar cells [13].

Chemical compound and disease context of TPD52

• NIDDM had no effect on either PC-1 content or glucose transport for any given level of obesity [14].
• Two hamster pancreatic cancer cell lines, PC-1 and PC1.0, established from N-nitrosobis(2-oxopropyl)amine-induced pancreatic ductal/ductular adenocarcinomas exhibit different growth patterns [15].
• The active site is also not in the conformation observed in the complex of another class A beta-lactamase, that of Staphylococcus aureus PC1, with the same phosphonate [Chen, C. C. H., et al. (1993) J. Mol. Biol. 234,165-178] [16].
• We then tested the relative in vivo antitumor activities of dietary farnesol, geraniol, and perillyl alcohol against transplanted PC-1 hamster pancreatic adenocarcinomas [17].
• Two pancreatic cancer cell lines, the highly invasive and metastatic cell line PC-1.0 and the weakly invasive and rarely metastatic cell line PC-1, were established from a pancreatic ductal carcinoma induced by N-nitrosobis (2-oxopropyl) amine in a Syrian golden hamster [18].

Biological context of TPD52

• The human D52 locus has been previously mapped to chromosome 8q21, and using in situ mapping in the present study, a human D53 locus was mapped to chromosome 6q22-q23 [19].
• TPD52 therefore represents a novel molecular marker in ovarian cancer, which is broadly expressed across the different histologic subtypes and whose upregulation frequently reflects increased TPD52 copy number [2].
• In an independent cohort of stage III serous carcinomas (n = 18), we also directly compared in situ TPD52 expression using immunohistochemistry and TPD52 copy number using interphase FISH analyses [2].
• Thus, D52-like proteins appear to exert and/or regulate their activities through specific interactions with other D52-like proteins, which in turn may be intrinsic to potential roles of these molecules in controlling cell proliferation [20].
• D52-like gene transcripts are subject to alternative splicing, with sequences encoding a region termed insert 3 being affected in all three D52-like genes [21].

Anatomical context of TPD52

• Our study has therefore identified a novel member of the MAL proteolipid family and potentially implicates TPD52-like proteins in vesicle transport [22].
• Tumor protein D52 (TPD52): a novel B-cell/plasma-cell molecule with unique expression pattern and Ca(2+)-dependent association with annexin VI [13].
• TPD52 expression pattern in normal and neoplastic B cells was unique [13].
• These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype [2].
• Monoclonal anti-PrLZ antibodies were produced and intense immunohistochemical staining of PrLZ was observed in prostate epithelial cells in intraepithelial neoplasia and prostate cancer, whereas lower-level staining was detected in normal and benign epithelial components of the prostate gland [1].

Associations of TPD52 with chemical compounds

• Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)/mass-spectrometry analysis identified the 28-kDa protein as human tumor protein D52 (TPD52), whose expression had been previously described only in normal and neoplastic epithelia [13].
• Since D52-like protein sequences are all predicted to contain a coiled-coil domain, we used the yeast two-hybrid system and glutathione S-transferase pull-down assays to investigate whether homo- and/or heteromeric interactions occur between D52-like proteins [20].
• Furthermore, our studies suggest that TPD52 protein levels may be regulated by androgens, consistent with the presence of androgen response elements in the upstream promoter of TPD52 [23].
• These results suggest that cell motility of low-invasive PC-1 cells is under control through cyclic AMP-dependent protein kinase A, while the protein kinase C pathway seems favorable for high-invasive PC-1.0 cells to maintain the continuously enhanced cell motility responsible for their high invasiveness [24].
• Interleukin 1 beta suppresses transforming growth factor-induced inorganic pyrophosphate (PPi) production and expression of the PPi-generating enzyme PC-1 in human chondrocytes [12].

Other interactions of TPD52

• Identification of MAL2, a novel member of the mal proteolipid family, though interactions with TPD52-like proteins in the yeast two-hybrid system [22].
• The identified hD54 cDNAs predicted three hD54 isoforms, suggesting that alternatively-spliced transcripts may be produced from D52-like genes [25].
• Although its expression was enhanced by androgens in androgen receptor-expressing cells, PrLZ was detected in all of the human prostate cancer cell lines, regardless of androgen receptor status [1].
• Using differential display method, we have isolated and characterized a novel gene, N8, encoding an approximately 24 kDa protein [26].
• N8 protein is capable of forming a homodimer or multimeter in vitro [27].

Analytical, diagnostic and therapeutic context of TPD52

• Specific B28p reactivity with TPD52 was confirmed by immunostaining/immunoblotting of TPD52-transfected cells [13].
• Fluorescence in situ hybridization on tissue microarrays confirmed TPD52 amplification in prostate cancer epithelia [23].
• Based on a meta-analysis of gene expression microarray data from multiple prostate cancer studies (D. R. Rhodes et al., Cancer Res 2002;62:4427-33), a candidate oncogene, Tumor Protein D52 (TPD52), was identified in the 8q21 amplicon [23].
• Increased copy number (ICN) was measured using Southern blot analyses in 3/32 human breast carcinomas at hD52, and the related hD54 gene in 20q13.2-q13 [28].
• This was confirmed by directly sequencing reverse transcriptase-polymerase chain reaction (RT-PCR) products amplified from D52-like gene transcripts expressed in developing and adult rat tissues, and by performing sequence analyses of the expressed sequence tag divisions of nucleotide databases [25].

References