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K Kadomatsu

Publications and source records attributed to K Kadomatsu.

103 records · Page 6Linked to original sources
PubMed1990

A retinoic acid responsive gene, MK, produces a secreted protein with heparin binding activity.

MK is a gene whose expression increases transiently during retinoic acid-induced differentiation of embryonal carcinoma cells. MK polypeptide was secreted by differentiating HM-1 embryonal carcinoma cells and by L-cells transfected with an MK cDNA under the control of the beta-actin promoter and Rous sarcoma virus enhancer. MK polypeptide was found to have heparin binding activity. Conditioned medium of the transfected L-cells promoted growth of PC-12 pheochromocytoma cells. These findings support the view that MK polypeptide is a secreted factor involved in regulation of growth and differentiation.

Animals↗
PubMed1990

A retinoic acid-responsive gene, MK, found in the teratocarcinoma system. Heterogeneity of the transcript and the nature of the translation product.

A newly identified gene, MK, is transiently expressed in the early stages of embryonal carcinoma cell differentiation and in the mid-gestation period of mouse embryogenesis (Kadomatsu, K., Tomomura, M., and Muramatsu, T. (1988) Biochem. Biophys. Res. Commun. 151, 1312-1318). Analysis of various MK cDNA clones revealed differences in the 5'-region. So far three classes of cDNA clones (MK1, MK2, and MK3) have been identified; they were different in the 5'-untranslated region but shared the rest of the sequence. Ribonuclease protection, RNA blotting, and primer extension revealed that MK2-type RNA was the major MK RNA in retinoic acid-treated embryonal carcinoma cells. In addition, the number of A residues in an oligo(A) stretch in the 5'-side of the common sequence differed from 9 to 29. The number was 9 in the most frequent cases, when the putative MK polypeptide had a molecular weight of about 15,500 and had a signal peptide-like sequence. Hybrid selected MK RNA yielded the predicted polypeptide upon in vitro translation. When pancreatic microsomal membranes were included in the translation system, the translation product of MK RNA was processed and entered into the lumen of the membranes. These results suggest that the product of the MK gene is an extracellular polypeptide.

Amino Acid Sequence↗
PubMed1990

Structure of a retinoic acid-responsive gene, MK, which is transiently activated during the differentiation of embryonal carcinoma cells and the mid-gestation period of mouse embryogenesis.

MK is a gene that is expressed temporarily during the early stages of retinoic acid-induced differentiation of embryonal carcinoma (EC) cells and during the mid-gestation period of mouse embryogenesis. The 5'-regions of MK cDNAs and their mRNAs are heterogeneous; so far three kinds of MK cDNAs (MK1, MK2, and MK3) have been isolated. The MK gene was cloned from a genomic DNA library of a BALB/c mouse, and its structure was elucidated. 5'-Region sequences specific for MK1, MK2, and MK3 were arranged in the order of MK3, MK2, and MK1. Then, there was a sequence common to all MK cDNAs consisting of four exons. The results indicate that different species of MK mRNA are generated by the use of alternative promoters and different modes of splicing.

Amino Acid Sequence↗
PubMed1990

Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas.

Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N-myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression.

Cell Differentiation↗
PubMed1990

A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis.

A newly identified gene MK is transiently expressed in early stages of retinoic acid-induced differentiation of embryonal carcinoma cells (Kadomatsu, K., M. Tomomura, and T. Muramatsu, 1988. Biochem. Biophys. Res. Commun. 151:1312-1318). MK gene has been predicted to code a polypeptide that is rich in basic amino acids and cysteine and is not related to any other peptides so far reported. In the present study, we investigated MK expression during mouse embryogenesis by in situ hybridization. The MK transcript was detected all over the embryo proper of the 7-d embryo, while it was not detectable in the 5-d embryo. The ubiquitous expression continued in the 9-d embryo proper. On the 11th-13th d of gestation, the sites where MK gene was intensely expressed became progressively restricted; these sites were the brain ectoderm around the lens and brain ventricles, the anterior lobe of the pituitary gland, the upper and lower jaw, the caudal sclerotomic half of vertebral column, the limbs, the stomach, and the epithelial tissues of the lung, the pancreas, the small intestine, and the metanephros. These areas include the region where secondary embryonic induction is prominent. In the 15-d embryo, only the kidney expressed MK significantly. These data suggest that MK gene plays a fundamental role in the differentiation of a wide variety of cells; MK gene may also play some specific roles in generation of epithelial tissues, and remodeling of mesoderm.

Animals↗
PubMed1990

Developmentally regulated expression of embigin, a member of the immunoglobulin superfamily found in embryonal carcinoma cells.

Embigin is a member of the immunoglobulin superfamily found in embryonal carcinoma cells. The present study deals with embigin gene expression in adult and embryonic cells. By RNA blot analyses, high levels of embigin mRNA were detected in embryonal carcinoma cells with different differentiation potentials, namely F9 and PCC4 cells. Similar or slightly higher levels of the RNA were detected in the embryonic and extraembryonic portions of 9-day mouse embryos. When F9 cells were induced to differentiate by treatment with retinoic acid and dibutyryl cyclic AMP for 2-5 days, the RNA level increased significantly. On the other hand, embigin mRNA dramatically dropped to almost background levels in embryos, from 11 days postcoitus (p.c.). Many organs of adult mice expressed only low levels of embigin mRNA, but considerable amounts of the transcript were found in the ovary and also in the uterus of pregnant mice (4 days p.c. and 12 days p.c.). In situ hybridization experiments revealed large amounts of embigin RNA in the embryo from 7 to 9 days p.c. The visceral endoderm of 7-day embryos, and the brain, visceral yolk sac and presumptive foregut of 9-day embryos were the sites where intense signals of embigin RNA were localized.

Amino Acid Sequence↗
PubMed1988

cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis.

By the differential hybridization technique, we isolated a cDNA clone, MK1, whose RNA level increased in early stages of retinoic acid-induced differentiation of embryonal carcinoma cells. The amount of MK1 RNA progressively decreased in the later stages of the differentiation. In mouse embryos, MK1 RNA was abundant in mid-gestation stages (Day 8 to Day 11) and decreased thereafter. The corresponding RNA was 1.0 killobase in size. From the nucleotide sequence, MK1 gene was predicted to code a polypeptide of molecular weight 9,971, which was rich in basic amino acids.

Animals↗
PubMedDate not supplied

Expression of the midkine gene in human hepatocellular carcinomas.

BACKGROUND/AIMS: Aberrant expression of Midkine (MK) has been found in various human carcinomas including hepatocellular carcinoma (HCC). The aim of study is to identify the incidence of MK expression in tumor and surrounding non-tumor tissues of the liver, and to find the correlation of MK expression with other tumor markers. METHODOLOGY: Liver tissues were obtained from 16 patients with HCC and 4 with metastatic liver cancer. Background diseases of the HCC patients include liver cirrhosis and chronic hepatitis of type B or C. RNA was prepared from both cancerous and surrounding non-cancerous tissues, and analyzed for the presence of MK mRNA by RT-PCR, PCR-Southern blot, and Northern blot analysis. RESULTS: MK expression was detected in 12 (75%) of 16 HCCs by PCR-Southern blot analysis, the most sensitive of the 3 methods. Three of 9 surrounding cirrhotic tissues were weakly positive for MK expression, and none of chronic hepatitis and 4 normal tissues were negative. No significant difference was found in clinical and pathological parameters between MK negative and positive cases. Among metastatic cancers, 1 of gastric origin was positive for MK expression, but 1 each of chorangiocellular, gall bladder, and gastrinoma origin was negative. CONCLUSIONS: These results suggest that MK is expressed in the majority of HCC tissues and rarely in surrounding tissues in chronic liver diseases.

Aged↗
PubMedDate not supplied

Polyadenylation signal facilitates the expression of foreign gene that is driven by an internal promoter located in the reverse orientation to long terminal repeat of retrovirus.

We examined whether the presence of a polyadenylation [poly(A)] signal in a retrovirus vector could affect the expression level of exogenous gene(s) that was controlled by an internal promoter. Three suicide genes were placed under a promoter of the human midkine gene, whose expression is elevated in lung cancer cells. Orientation of the internal transcriptional unit was designed to be opposite to the viral long terminal repeat. Expression of each suicide gene was greater in ecotropic packaging cells transfected with a retrovirus vector without a poly(A) signal than in those with a poly(A)-containing vector. Sensitivity to ganciclovir, a prodrug that becomes an active drug by herpes simplex virus-thymidine kinase, was significantly improved in retrovirally transduced lung cancer cells compared with wild-type cells. However, the sensitivity was much greater in the cells transduced with poly(A)-containing vector than in those with poly(A)-deleted construct. The presence of a poly(A) signal downstream of exogenous gene(s) therefore favors the expression of foreign gene(s) driven by an internal promoter.

Biotransformation↗