Disease relevance of MAGED2

• In a search for genes involved in X-linked mental retardation we have analyzed the expression pattern and genomic structure of human MAGED2 [1].
• In addition, we isolated a gene we call breast cancer associated gene-1 that was expressed almost exclusively in fresh breast cancer tissue and not in normal mammary epithelium or breast cancer cell lines [2].
• We were unable to detect expression of breast cancer associated gene-1 in cell lines from melanoma, renal cell carcinoma, lymphoma, or leukemia [2].
• MAGE-D2 and MTA1 message were significantly elevated (> 10-fold, P < 0.01) in the malignant and goblet cell adenocarcinoid tumors but not in the appendicitis-associated carcinoids or normal mucosa [3].
• MAGE-D2 and MTA1 were increased (P < .05) in primary tumors and metastases and overexpressed in carcinomas [4].

High impact information on MAGED2

• We have isolated genomic and cDNA clones of Brca1, a mouse homolog of the recently cloned breast cancer-associated gene, BRCA1 [5].
• A homologue of the breast cancer-associated gene BARD1 is involved in DNA repair in plants [6].
• FoxM1-deficient cells display reduced expression of the base excision repair factor X-ray cross-complementing group 1 (XRCC1) and breast cancer-associated gene 2 (BRCA2), the latter of which is involved in homologous recombination repair of DNA double-strand breaks [7].
• In this study, we examined whether the breast cancer-associated gene 2 (BCA2), a novel RING domain protein, has E3 ubiquitin ligase activity and investigated its expression status in breast tumors [8].
• We investigated the expression pattern of the breast cancer associated gene LIV-1 on mRNA and protein level in 111 human breast cancer patients by in situ hybridization as well as immunohistochemistry and focused on the unknown potential of LIV-1 expression levels as a prognostic marker [9].

Biological context of MAGED2

• Five SNPs in the coding region of human MAGED2 were characterized and their allele frequencies determined in a German and Turkish population [1].
• Further sequence analysis of the 4.1kb transcript revealed at least a 509 nucleotide sequence exactly complementary to the 2.0kb MAGE D2 mRNA sequence [10].
• The MAGE-D proteins contain an additional, fourth domain, which in the case of MAGE-D3 coincides with trophinin, a separate molecule described previously as an adhesion molecule that participates in embryo implantation [11].
• Comparative expression analysis of the MAGED genes during embryogenesis and brain development [12].
• Cumulative evidence indicates that breast cancer-associated gene 1 (BRCA1) participates in DNA damage repair and cell-cycle checkpoint control, serving as a tumor susceptibility gene to maintain the global genomic stability [13].

Anatomical context of MAGED2

• CONCLUSIONS: These data demonstrate that malignant APCs and goblet cell adenocarcinoids have elevated expression of NAP1L1, MAGE-D2, and MTA1 compared with appendiceal carcinoids identified at surgery for appendicitis [3].
• A novel messenger ribonucleic acid homologous to human MAGE-D is strongly expressed in rat Sertoli cells and weakly in Leydig cells and is regulated by follitropin, lutropin, and prolactin [14].
• As MAGE-D is present in both the seminiferous compartment and interstitium and hormonally regulated in each, it is possible that it has specific functions in each compartment during the development and the maintenance of the testis [14].
• Interestingly, MAGE-D was also detected for the first time in the female gonad by Northern blotting [14].
• In the seminiferous tubules, the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression has been shown to be restricted to germ cells [14].

Associations of MAGED2 with chemical compounds

• Most of the BCG1-controlled genes are still expressed in adenylate cyclase (bac) mutants in planta, suggesting that BCG1 is involved in at least one additional signaling cascade in addition to the cAMP-depending pathway [15].
• Application of exogenous cyclic AMP restored the wild-type growth pattern of bcg1 mutants, but not the protease secretion, implicating an essential role of BCG1 in different signaling pathways [16].

Other interactions of MAGED2

• In contrast to the genes of the MAGE-A, MAGE- B and MAGE-C clusters, MAGED2 is expressed ubiquitously [1].
• Expression of the breast cancer associated gene pS2 and the pancreatic spasmolytic polypeptide gene (hSP) in diffuse type of stomach carcinoma [17].
• The epithelial-specific ETS transcription factor ESX/ESE-1/Elf-3 modulates breast cancer-associated gene expression [18].
• These results suggest that MAGE-D and -E1 may be evolutionarily distant from other members of the MAGE family, and the two may be ancestral genes for the others [19].
• The samples were tested for mammaglobin and three breast cancer-associated gene transcripts by a multigene real-time RT-PCR assay and for serum mammaglobin protein by a sandwich ELISA assay [20].

Analytical, diagnostic and therapeutic context of MAGED2

• Surprisingly, in situ hybridization of lung tissue demonstrated positive hybridization signals with sense, but not antisense, MAGE D2-specific cRNA probes [10].
• In a pilot study, porous barrier density gradient centrifugation and multimarker real-time RT-PCR enabled our laboratory to detect breast cancer-associated gene overexpression in 13 of 20 (65%) stage IV breast cancer patients [21].
• The EMMA method is compared to denaturing HPLC (DHPLC) in a large-scale study of mutations in the breast cancer-associated gene BRCA2, involving 4655 DNA amplicons from 94 patients [22].
• To identify signal transduction pathways of the gray mold fungus Botrytis cinerea involved in host infection, we used heterologous hybridization and a polymerase chain reaction (PCR)-based approach to isolate two genes (bcg1 and bcg2) encoding alpha subunits of heterotrimeric GTP-binding proteins [16].
• Damage to DNA results in activation of damage response pathways, as indicated by Western blotting using antibodies specific for p53 and breast cancer-associated gene 1 (BRCA1) phosphorylation [23].

References