title: Apoptotic cell death of high polyploid cells in a cultured sarcoma cell line.
abstract: It is well known that DNA-ploidy is useful independent prognosticator of malignancy. However, the biological significance of polyploid cells and the relation between polyploidy and prognosis is not well understood. We analyzed DNA ploidy by flow cytometry in Meth-A cells (a cultured sarcoma cell line) after treatment with K252a, a protein kinase inhibitor, and showed induction of polyploidization. Apoptotic cell death of the high polyploid cells was verified by flow cytometry, morphological observation and gel analysis of DNA integrity. Expression of tumor-suppressor nuclear protein p53 investigated by immunohistochemistry was increased 10-fold or more in cells with 16C (C = haploid DNA content) relative to cells with 2C, suggesting that the overexpression of p53 was involved in the apoptosis. These results may be of clinical relevance since it has been known that both DNA ploidy and p53 expression have prognostic significance.
authors.affiliation: Division of Basic Science, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan. zong3961@kanazawa-med.ac.jp
authors.forename: Z P
authors.initials: ZP
authors.lastname: Zong
authors.forename: K
authors.initials: K
authors.lastname: Fujikawa-Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Ota
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: A L
authors.initials: AL
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Tanino
authors.forename: S
authors.initials: S
authors.lastname: Odashima
mesh_terms: D000818:Animals; D017209:Apoptosis; D002227:Carbazoles / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D026121:Indole Alkaloids; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D011123:Polyploidy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002227:Carbazoles; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D016159:Tumor Suppressor Protein p53; D008748:Methylcholanthrene; C049985:staurosporine aglycone; D011493:Protein Kinase C