Disease relevance of Mia1

• DNase I hypersensitivity assays comparing expressing and nonexpressing cells indicate that the chromatin structure surrounding Cdrap/Mia is not greatly altered for transcription [1].
• MIA/CD-RAP is a small, soluble protein secreted from malignant melanoma cells and from chondrocytes [2].
• As an approach to define the transcriptional regulatory domains responsible for induction of chondrocyte activity in vivo, we generated transgenic mice harboring various fragments of the mouse CD-RAP promoter linked to the Escherichia coli beta-galactosidase gene [3].
• Elsewhere, we demonstrated that MIA PaCa2 cultured cells secrete a soluble factor responsible for reduced glucose tolerance induced in SCID mice [4].
• Functional role of melanoma inhibitory activity in regulating invasion and metastasis of malignant melanoma cells in vivo [5].
• Among these genes, we focused our attention on the Mia/Cd-rap gene, whose expression was essentially suppressed in all of the pituitary adenomas tested by the microarray [6].

High impact information on Mia1

• It is thought that interaction between MIA/CD-RAP and specific epitopes in extracellular matrix proteins regulates the attachment of tumor cells and chondrocytes [2].
• The full-length FGFR1-IIIb cDNA was generated and stably expressed in PANC-1 and MIA PaCa-2 pancreatic cancer and TAKA-1 pancreatic ductal cells [7].
• Data from incubations with synthetic lipoxygenase products revealed that (a) the culture of mouse marrow cells in the presence of varying amounts of purified CSF-I (Mia PaCa 2) with a low concentration (5 micrograms/ml) of nordihydroguaretic acid consistently suppressed CSF-induced colony formation by approximately 40-50% [8].
• CCAAT/enhancer-binding proteins beta and delta mediate the repression of gene transcription of cartilage-derived retinoic acid-sensitive protein induced by interleukin-1 beta [9].
• Compared with MIA PaCa-2/vector cells, MIA PaCa-2/RII cells showed a greater than 3-fold increase in apoptosis after radiation [10].

Chemical compound and disease context of Mia1

• MIA (melanoma inhibitory activity) has been previously isolated from the tissue culture supernatant of melanoma cell lines as an autoregulatory activity, inhibiting thymidine incorporation [5].
• This study evaluated in vitro and in vivo effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with gemcitabine, using two human pancreatic cancer cell lines, S2VP10 and MIA PaCa-2 [11].
• A human pancreatic adenocarcinoma cell line, Mia PaCa-2, was incubated for 18 hours with 5 micromol/L of rofecoxib (Vioxx), a selective COX-2 inhibitor [12].
• With this assay, androgen receptors were detected in five fresh human pancreatic adenocarcinoma specimens (three male), two pancreatic cancer cell lines (Mia PaCa 2 and Ger), one xenograft tumor which responded to androgens, five specimens of normal adult pancreas (two male), and a pool of fetal pancreatic tissue [13].

Biological context of Mia1

• We therefore subcloned 1.4 kb of the murine MIA promoter and a series of 5' deletion constructs into a luciferase reporter plasmid and identified the most active cis-regulatory element between nucleic acids -230 and -130 [14].
• Characterization of a transcription factor binding site, specifically activating MIA transcription in melanoma [14].
• For three genes, Cdrap, Tgfbi, and Col15a1, we observed strikingly similar expression in the developing kidneys and lungs, which both undergo branching morphogenesis [15].
• The 2.2-kb promoter of cartilage-derived retinoic acid-sensitive protein controls gene expression in cartilage and embryonic mammary buds of transgenic mice [3].
• The cartilage transgene expression pattern is consistent with that of endogenous CD-RAP gene expression [3].

Anatomical context of Mia1

• To determine whether CD-RAP/MIA is associated with tumors of cartilage, mRNAs from a variety of rodent tissues and cell lines were screened [16].
• Taken together, our data indicate that MIA/CD-RAP is essentially required for formation of the highly ordered ultrastructural fiber architecture in cartilage and may have a role in regulating chondrocyte matrix interactions [2].
• Preliminary studies of the human MIA gene provided evidence that the promoter is specifically activated in melanoma cells but is silent in nonmelanocytic cells and benign melanocytes [14].
• The finding of transient CD-RAP expression in mammary buds suggests that it may play a role in the organogenesis of mammary glands [3].
• The intracellular mechanism of insulin resistance was investigated in isolated and perfused rat hepatocytes incubated with MIA PaCa2 conditioned medium [4].

Associations of Mia1 with chemical compounds

• Lactate production was reduced compared to hepatocytes incubated with control medium while 1,2-DAG was increased and PKC was activated in the hepatocytes incubated with MIA PaCa2 conditioned medium [4].
• In chondrocytes, CD-RAP is down-regulated by retinoic acid [17].
• In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage [18].
• Actions of monoiodoacetic acid (MIA) as a sulfhydryl reagent on the different stages of the T cell receptor (TCR)-mediated signal transduction were examined [19].
• The MIA-promoted TCR-mediated IL-2 production actually required signal transduction that could be inhibited by cyclosporin A, genistein, or H-7 [19].

Physical interactions of Mia1

• We show here that Sox9 protein is able to bind to a SOX consensus sequence in the CD-RAP promoter [20].

Other interactions of Mia1

• Immunoreactivities of type II collagen and CD-RAP were higher in growth plate than in either the articular or meniscal cartilages and correlated positively with Sox9 protein [21].
• In cartilage, a number of studies indicate that Sox transcription factors are critical positive regulators in genes such as COL2A1, COL9A2, COL11A2, aggrecan, and CD-RAP [22].

Analytical, diagnostic and therapeutic context of Mia1

• The complete absence of MIA/CD-RAP mRNA and protein expression was demonstrated by reverse transcriptase, Western blot analysis, and enzyme-linked immunosorbent assay measurements of whole-embryo extracts [2].
• MIA (melanoma inhibitory activity) promoter mediated tissue-specific suicide gene therapy of malignant melanoma [23].
• Northern blot analysis revealed similar changes in CD-RAP and type II collagen mRNA levels [24].
• Cartilage-derived retinoic acid-sensitive protein (CD-RAP) and mRNA were examined in the mouse fracture model by immunohistochemistry and Northern blot analysis and compared with the expression of type II collagen [24].
• RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2 [18].

References