Genomic Structure of Human Midkine (MK), a Retinoi1c Acid-Responsive Growth/Differentiation Factor1

Abstract

Midkine (MK) is a product of a retinoic acid-responsive gene and a new heparin-binding growth/differentiation factor. The coding sequence of human MK was located on 1.5 kb DNA segment. The structure of the cloned human MK gene was determined and compared with that of the mouse gene. The coding sequence was divided into 4 exons, and each exon and exon-intron boundary was highly homologous to those of the mouse. Furthermore, 170 bases in the upstream region of the putative transcription initiation sites and 3 blocks of 200-350 bases in regions further upstream were highly conserved. These sequences are likely to be involved in developmentally regulated expression of MK.

Synergy between expression of fusogenic membrane proteins, chemotherapy and facultative virotherapy in colorectal cancer

“…27 The titers (GTU/ml) of the Ad.H/F and HSV.H/F vectors, both encoding GFP by a second transcription unit, were determined in the presence of the synthetic fusion-inhibitory peptide by flow cytometry 59 on DLD-1, HT-29, PCC #1, A549 and 293 cells. The activity of the Ad.COXDMK and G47D vectors were determined on the same panel of cells by TCID 50 . 27 Viral transduction efficiency DLD-1, HT-29, PCC #1, PCC #2 and 293 cells were seeded at a concentration of 1 Â 10 3 cells/well in 100 ml into 96-well flat-bottom culture plates.…”

“…Cells were treated with serial dilutions of each drug individually or with a fixed ratio of both drugs simultaneously at doses that corresponded to i, g, l, h, 1 and 1i times the respective ED 50 . When the two drugs were administered at a fixed ratio, the dose of the combination required to produce fractional survival (f) could be separated into the components (D) 1 and (D) 2 26,60 When the concentration-effect relationship follows the principle of mass action, the median-effect plot should be linear.…”

“…Animals treated with the oncolytic viruses or the measles virus FMG encoding vectors alone or in combination with FOLFOX received intratumoral in 100 ml PBS on day 0, day 1 and day 2, 2 Â 10 8 TCID 50 or GTU determined on HT-29, respectively. Animals treated with the oncolytic viruses in combination with Ad.H/F or HSV.H/F received per treatment cycle 1 Â 10 8 TCID 50 plus 1 Â 10 8 GTU (determined on HT-29) alone or in combination with FOLFOX.…”

Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions

“…These changes may trigger signaling pathways that lead to MDK induction, as fatty acids act as specific ligands for some nuclear receptors, such as peroxisome proliferatoractivated receptor (PPAR) (Schoonjans et al, 1996). Although the promoter region of the MDK gene does not possess any direct responsive element for PPAR, it does contain specific elements, including the steroid/ thyroid hormone receptor-binding site (TRE) (Uehara et al, 1992). Because PPAR can form a heterodimer with a thyroid hormone receptor (Bogazzi et al, 1994), the element might have a function in the ACSL5-dependent induction of the MDK gene.…”

A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the α-fetoprotein promoter

“…The 2335-bp genomic DNA fragment of the MK gene (À2285/ þ 50, þ 1 corresponds to the transcription start site) (Uehara et al, 1992) was cloned into the pGL2-basic vector (Promega, Madison, WI, USA) that contained the firefly luciferase gene without any promoter sequences (MK2.3-luc). MK2.3kb-luc DNA was digested with XhoI/Eco47III to produce the 609-bp fragment-linked firefly luciferase genes (MK0.6-luc).…”