Truncated midkine correlates with sensitivity to anticancer drugs and malignancy in human tumor cell line.
Midkine (MK) is a heparin binding growth factor having functions of neurite-outgrowth, mitogenesis and tissue repair. This molecule is involved in tumor growth and metastasis. The MK molecule consists of five exons, but there is a truncated isoform, lacking exon 3. We established SW13 cells transfected with the human truncated MK cDNA. These cells were induced to undergo apoptosis by anticancer agents, cisplatin, etoposide (ETP), mitomycin C (MMC) and paclitaxel (PAX). Truncated midkine (tMK) suppressed cell death and helped the cells to be viable. When the cells were cultured on dishes coated with extracellular matrix molecules, spontaneous detachment occurred in the tMK expressing cells. Also tMK enhanced cell invasion. These results suggest that expression of tMK has cell-protective functions and plays important roles in carcinogenesis and malignancy. Furthermore, it is suggested that tMK has a greater ability of malignant transformation than full-length MK. Whether tMK is expressed or not will be useful information for improving cancer chemotherapy.
Akuzawa
Natsuyo
N
Department of Biological and Chemical Engineering, Faculty of Engineering, Gunma University, Kiryu, Gunma, Japan.
Nobata
Shigenori
S
Shinozawa
Takao
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D000078792:Midkine; D016685:Mitomycin / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000970:Antineoplastic Agents; D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D020033:Protein Isoforms; D000078792:Midkine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D016685:Mitomycin; D005047:Etoposide; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D017239:Paclitaxel; D002945:Cisplatin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one