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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sasaki, Y. Articles by Nakao, K. Search for Related Content PubMed PubMed Citation Articles by Sasaki, Y. Articles by Nakao, K. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 6 (September 15), 1999: pp. 1952-1960 Production of Thrombopoietin by Human Carcinomas and Its Novel Isoforms Yutaka Sasaki, Takayuki Takahashi, Hiroshi Miyazaki, Atsushi Matsumoto, Takashi Kato, Kishiko Nakamura, Sumiko Iho, Yoshiaki Okuno, and Kazuwa Nakao From the Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan; the Department of Hematology and Clinical Immunology, Kobe City General Hospital, Kobe, Japan; the Pharmaceutial Reseach Laboratory, Kirin Brewery Co, Takasaki, Japan; the College of Medical Technology, Kyoto University, Kyoto, Japan; and the Department of Immunology and Medical Zoology, Faculty of Medicine, Fukui Medical University, Fukui, Japan. Thrombocytosis is occasionally seen in patients with carcinomas and has been assumed to be attributable to interleukin-6 or granulocyte-macrophage colony-stimulating factor produced by carcinoma cells. In this study, we clarified whether thrombopoietin (TPO) is involved in carcinoma-associated thrombocytosis. Expression of TPO mRNA was observed in the majority of 27 carcinoma cell lines as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). There were 6 PCR products differing in size; sequence analysis showed the full-length TPO mRNA (TPO-1), 12- and 116-bp deleted variants (TPO-2 and TPO-3, respectively), and 3 novel isoforms (197- and 128-bp deleted forms and a 60-bp insert form of TPO-3; named TPO-4, TPO-5, and TPO-6, respectively). Of 27 lines, 24 expressed TPO-1 mRNA with various other isoforms. Culture supernatants of COS-1 cells transfected with TPO-5 or TPO-6 cDNA did not promote the proliferation of TPO-responsive cells, whereas Western blot analysis on the cell lysates demonstrated TPO-5 but not TPO-6 protein, suggesting poor extracellular secretion (TPO-5) or poor protein synthesis (TPO-6). TPO protein was detected in 10-fold concentrated culture supernatants of cells of these carcinoma lines, with a median concentration of 0.38 fmol/mL as evaluated by enzyme-linked immunosorbent assay. High blood TPO levels were observed with a median value of 3.46 fmol/mL (range, 0.34 to 8.67 fmol/mL) in patients with advanced carcinomas associated with thrombocytosis. These results indicate that thrombocytosis in patients with carcinomas might be caused, at least in part, by TPO produced by carcinoma cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Romano, R. Marcucci, and F. E. Baralle Splicing of constitutive upstream introns is essential for the recognition of intra-exonic suboptimal splice sites in the thrombopoietin gene Nucleic Acids Res., February 15, 2001; 29(4): 886 - 894. [Abstract] [Full Text] [PDF]

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