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. 1987 May;6(5):1213–1218. doi: 10.1002/j.1460-2075.1987.tb02356.x

Induction of platelet-derived growth factor gene expression during megakaryoblastic and monocytic differentiation of human leukemia cell lines.

R Alitalo, L C Andersson, C Betsholtz, K Nilsson, B Westermark, C H Heldin, K Alitalo
PMCID: PMC553921  PMID: 3475202

Abstract

Platelet-derived growth factor (PDGF) is one of the most important polypeptide growth factors in human serum. It is composed of two polypeptide chains linked by disulfide bonds. The B-chain is encoded by the c-sis proto-oncogene, which is expressed in several malignant and non-malignant cells including K562 cells differentiating towards megakaryoblasts. Expression of the A-chain has been reported to occur in human solid tumor cell lines independently of c-sis expression. We report here the non-coordinate expression of the A- and B-chains in human leukemia cell lines. The PDGF-A and B-chain (c-sis) RNA expression as well as secretion of PDGF polypeptides are induced in the K562 cell line upon induction of megakaryoblastic differentiation with 12-O-tetradecanoyl phorbol-13-acetate (TPA) whereas erythroid differentiation induced with sodium butyrate is accompanied by c-sis expression only. Simultaneously with megakaryoblastic differentiation the RNA level for another platelet protein, the transforming growth factor-beta was also increased, but in a complex manner. The promyelocytic leukemia cell line HL-60 does not express PDGF-A RNA, whereas the promonocytic cell line U937 does. Preferential induction of the A-chain RNA is obtained in both cell lines after treatment with TPA which causes monocytic differentiation. PDGF-A expression in HL-60 cells is also observed after treatment with the tumor necrosis factor-alpha but granulocytic differentiation of HL-60 cells induced with dimethyl sulfoxide or the granulocyte colony-stimulating factor is not associated with PDGF gene expression.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson L. C., Jokinen M., Gahmberg C. G. Induction of erythroid differentiation in the human leukaemia cell line K562. Nature. 1979 Mar 22;278(5702):364–365. doi: 10.1038/278364a0. [DOI] [PubMed] [Google Scholar]
  2. Assoian R. K., Komoriya A., Meyers C. A., Miller D. M., Sporn M. B. Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 1983 Jun 10;258(11):7155–7160. [PubMed] [Google Scholar]
  3. Barnekow A., Gessler M. Activation of the pp60c-src kinase during differentiation of monomyelocytic cells in vitro. EMBO J. 1986 Apr;5(4):701–705. doi: 10.1002/j.1460-2075.1986.tb04270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barrett T. B., Gajdusek C. M., Schwartz S. M., McDougall J. K., Benditt E. P. Expression of the sis gene by endothelial cells in culture and in vivo. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6772–6774. doi: 10.1073/pnas.81.21.6772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
  6. Betsholtz C., Johnsson A., Heldin C. H., Westermark B., Lind P., Urdea M. S., Eddy R., Shows T. B., Philpott K., Mellor A. L. cDNA sequence and chromosomal localization of human platelet-derived growth factor A-chain and its expression in tumour cell lines. Nature. 1986 Apr 24;320(6064):695–699. doi: 10.1038/320695a0. [DOI] [PubMed] [Google Scholar]
  7. Bishop J. M. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. doi: 10.1016/s0092-8674(85)80098-2. [DOI] [PubMed] [Google Scholar]
  8. Colamonici O. R., Trepel J. B., Vidal C. A., Neckers L. M. Phorbol ester induces c-sis gene transcription in stem cell line K-562. Mol Cell Biol. 1986 May;6(5):1847–1850. doi: 10.1128/mcb.6.5.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Collins S. J., Groudine M. T. Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4813–4817. doi: 10.1073/pnas.80.15.4813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Collins S. J., Ruscetti F. W., Gallagher R. E., Gallo R. C. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci U S A. 1978 May;75(5):2458–2462. doi: 10.1073/pnas.75.5.2458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Collins T., Ginsburg D., Boss J. M., Orkin S. H., Pober J. S. Cultured human endothelial cells express platelet-derived growth factor B chain: cDNA cloning and structural analysis. Nature. 1985 Aug 22;316(6030):748–750. doi: 10.1038/316748a0. [DOI] [PubMed] [Google Scholar]
  12. Craig R. W., Bloch A. Early decline in c-myb oncogene expression in the differentiation of human myeloblastic leukemia (ML-1) cells induced with 12-O-tetradecanoylphorbol-13-acetate. Cancer Res. 1984 Feb;44(2):442–446. [PubMed] [Google Scholar]
  13. Dani C., Piechaczyk M., Audigier Y., El Sabouty S., Cathala G., Marty L., Fort P., Blanchard J. M., Jeanteur P. Characterization of the transcription products of glyceraldehyde 3-phosphate-dehydrogenase gene in HeLa cells. Eur J Biochem. 1984 Dec 3;145(2):299–304. doi: 10.1111/j.1432-1033.1984.tb08552.x. [DOI] [PubMed] [Google Scholar]
  14. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  15. Derynck R., Jarrett J. A., Chen E. Y., Goeddel D. V. The murine transforming growth factor-beta precursor. J Biol Chem. 1986 Apr 5;261(10):4377–4379. [PubMed] [Google Scholar]
  16. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  17. Fujisawa M., Kobayashi Y., Okabe T., Takaku F., Komatsu Y., Itoh S. Recombinant human granulocyte colony-stimulating factor induces granulocytosis in vivo. Jpn J Cancer Res. 1986 Sep;77(9):866–869. [PubMed] [Google Scholar]
  18. Gahmberg C. G., Ekblom M., Andersson L. C. Differentiation of human erythroid cells is associated with increased O-glycosylation of the major sialoglycoprotein, glycophorin A. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6752–6756. doi: 10.1073/pnas.81.21.6752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gahmberg C. G., Jokinen M., Andersson L. C. Expression of the major red cell sialoglycoprotein, glycophorin A, in the human leukemic cell line K562. J Biol Chem. 1979 Aug 10;254(15):7442–7448. [PubMed] [Google Scholar]
  20. Gee C. E., Griffin J., Sastre L., Miller L. J., Springer T. A., Piwnica-Worms H., Roberts T. M. Differentiation of myeloid cells is accompanied by increased levels of pp60c-src protein and kinase activity. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5131–5135. doi: 10.1073/pnas.83.14.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Goff S. P., Gilboa E., Witte O. N., Baltimore D. Structure of the Abelson murine leukemia virus genome and the homologous cellular gene: studies with cloned viral DNA. Cell. 1980 Dec;22(3):777–785. doi: 10.1016/0092-8674(80)90554-1. [DOI] [PubMed] [Google Scholar]
  22. Goustin A. S., Betsholtz C., Pfeifer-Ohlsson S., Persson H., Rydnert J., Bywater M., Holmgren G., Heldin C. H., Westermark B., Ohlsson R. Coexpression of the sis and myc proto-oncogenes in developing human placenta suggests autocrine control of trophoblast growth. Cell. 1985 May;41(1):301–312. doi: 10.1016/0092-8674(85)90083-2. [DOI] [PubMed] [Google Scholar]
  23. Grosveld G., Verwoerd T., van Agthoven T., de Klein A., Ramachandran K. L., Heisterkamp N., Stam K., Groffen J. The chronic myelocytic cell line K562 contains a breakpoint in bcr and produces a chimeric bcr/c-abl transcript. Mol Cell Biol. 1986 Feb;6(2):607–616. doi: 10.1128/mcb.6.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Heldin C. H., Wasteson A., Westermark B. Platelet-derived growth factor. Mol Cell Endocrinol. 1985 Mar;39(3):169–187. doi: 10.1016/0303-7207(85)90061-9. [DOI] [PubMed] [Google Scholar]
  25. Heldin C. H., Westermark B. Growth factors: mechanism of action and relation to oncogenes. Cell. 1984 May;37(1):9–20. doi: 10.1016/0092-8674(84)90296-4. [DOI] [PubMed] [Google Scholar]
  26. Heldin C. H., Westermark B., Wasteson A. Demonstration of an antibody against platelet-derived growth factor. Exp Cell Res. 1981 Dec;136(2):255–261. doi: 10.1016/0014-4827(81)90003-3. [DOI] [PubMed] [Google Scholar]
  27. Heldin C. H., Westermark B., Wasteson A. Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3664–3668. doi: 10.1073/pnas.78.6.3664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Konopka J. B., Watanabe S. M., Witte O. N. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984 Jul;37(3):1035–1042. doi: 10.1016/0092-8674(84)90438-0. [DOI] [PubMed] [Google Scholar]
  29. Kraft A. S., Smith J. B., Berkow R. L. Bryostatin, an activator of the calcium phospholipid-dependent protein kinase, blocks phorbol ester-induced differentiation of human promyelocytic leukemia cells HL-60. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1334–1338. doi: 10.1073/pnas.83.5.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
  31. Martinet Y., Bitterman P. B., Mornex J. F., Grotendorst G. R., Martin G. R., Crystal R. G. Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. Nature. 1986 Jan 9;319(6049):158–160. doi: 10.1038/319158a0. [DOI] [PubMed] [Google Scholar]
  32. May L. T., Helfgott D. C., Sehgal P. B. Anti-beta-interferon antibodies inhibit the increased expression of HLA-B7 mRNA in tumor necrosis factor-treated human fibroblasts: structural studies of the beta 2 interferon involved. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8957–8961. doi: 10.1073/pnas.83.23.8957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mitchell R. L., Henning-Chubb C., Huberman E., Verma I. M. c-fos expression is neither sufficient nor obligatory for differentiation of monomyelocytes to macrophages. Cell. 1986 May 23;45(4):497–504. doi: 10.1016/0092-8674(86)90281-3. [DOI] [PubMed] [Google Scholar]
  34. Müller R., Curran T., Müller D., Guilbert L. Induction of c-fos during myelomonocytic differentiation and macrophage proliferation. Nature. 1985 Apr 11;314(6011):546–548. doi: 10.1038/314546a0. [DOI] [PubMed] [Google Scholar]
  35. Müller R., Müller D., Guilbert L. Differential expression of c-fos in hematopoietic cells: correlation with differentiation of monomyelocytic cells in vitro. EMBO J. 1984 Aug;3(8):1887–1890. doi: 10.1002/j.1460-2075.1984.tb02063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Pantazis P., Sariban E., Kufe D., Antoniades H. N. Induction of c-sis gene expression and synthesis of platelet-derived growth factor in human myeloid leukemia cells during monocytic differentiation. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6455–6459. doi: 10.1073/pnas.83.17.6455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Reitsma P. H., Rothberg P. G., Astrin S. M., Trial J., Bar-Shavit Z., Hall A., Teitelbaum S. L., Kahn A. J. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature. 1983 Dec 1;306(5942):492–494. doi: 10.1038/306492a0. [DOI] [PubMed] [Google Scholar]
  38. Resnitzky D., Yarden A., Zipori D., Kimchi A. Autocrine beta-related interferon controls c-myc suppression and growth arrest during hematopoietic cell differentiation. Cell. 1986 Jul 4;46(1):31–40. doi: 10.1016/0092-8674(86)90857-3. [DOI] [PubMed] [Google Scholar]
  39. Robbins K. C., Devare S. G., Aaronson S. A. Molecular cloning of integrated simian sarcoma virus: genome organization of infectious DNA clones. Proc Natl Acad Sci U S A. 1981 May;78(5):2918–2922. doi: 10.1073/pnas.78.5.2918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
  41. Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rutherford T. R., Clegg J. B., Weatherall D. J. K562 human leukaemic cells synthesise embryonic haemoglobin in response to haemin. Nature. 1979 Jul 12;280(5718):164–165. doi: 10.1038/280164a0. [DOI] [PubMed] [Google Scholar]
  43. Saksela K., Bergh J., Lehto V. P., Nilsson K., Alitalo K. Amplification of the c-myc oncogene in a subpopulation of human small cell lung cancer. Cancer Res. 1985 Apr;45(4):1823–1827. [PubMed] [Google Scholar]
  44. Sariban E., Mitchell T., Kufe D. Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature. 1985 Jul 4;316(6023):64–66. doi: 10.1038/316064a0. [DOI] [PubMed] [Google Scholar]
  45. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  46. Shimokado K., Raines E. W., Madtes D. K., Barrett T. B., Benditt E. P., Ross R. A significant part of macrophage-derived growth factor consists of at least two forms of PDGF. Cell. 1985 Nov;43(1):277–286. doi: 10.1016/0092-8674(85)90033-9. [DOI] [PubMed] [Google Scholar]
  47. Shtivelman E., Lifshitz B., Gale R. P., Canaani E. Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. Nature. 1985 Jun 13;315(6020):550–554. doi: 10.1038/315550a0. [DOI] [PubMed] [Google Scholar]
  48. Siebert P. D., Fukuda M. Isolation and characterization of human glycophorin A cDNA clones by a synthetic oligonucleotide approach: nucleotide sequence and mRNA structure. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1665–1669. doi: 10.1073/pnas.83.6.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  50. Tabilio A., Pelicci P. G., Vinci G., Mannoni P., Civin C. I., Vainchenker W., Testa U., Lipinski M., Rochant H., Breton-Gorius J. Myeloid and megakaryocytic properties of K-562 cell lines. Cancer Res. 1983 Oct;43(10):4569–4574. [PubMed] [Google Scholar]
  51. Takeda K., Iwamoto S., Sugimoto H., Takuma T., Kawatani N., Noda M., Masaki A., Morise H., Arimura H., Konno K. Identity of differentiation inducing factor and tumour necrosis factor. 1986 Sep 25-Oct 1Nature. 323(6086):338–340. doi: 10.1038/323338a0. [DOI] [PubMed] [Google Scholar]
  52. Tetteroo P. A., Lansdorp P. M., Leeksma O. C., von dem Borne A. E. Monoclonal antibodies against human platelet glycoprotein IIIa. Br J Haematol. 1983 Nov;55(3):509–522. doi: 10.1111/j.1365-2141.1983.tb02166.x. [DOI] [PubMed] [Google Scholar]
  53. Tetteroo P. A., Massaro F., Mulder A., Schreuder-van Gelder R., von dem Borne A. E. Megakaryoblastic differentiation of proerythroblastic K562 cell-line cells. Leuk Res. 1984;8(2):197–206. doi: 10.1016/0145-2126(84)90143-7. [DOI] [PubMed] [Google Scholar]
  54. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  55. Westin E. H., Gallo R. C., Arya S. K., Eva A., Souza L. M., Baluda M. A., Aaronson S. A., Wong-Staal F. Differential expression of the amv gene in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(7):2194–2198. doi: 10.1073/pnas.79.7.2194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Zola H., McNamara P. J., Beckman I. G., Brooks D. A., Macardle P. J., Bradley J., Goodall K., Skinner J., Collins R., Berndt M. C. Monoclonal antibodies against antigens of the human platelet surface: preparation and properties. Pathology. 1984 Jan;16(1):73–78. doi: 10.3109/00313028409067914. [DOI] [PubMed] [Google Scholar]

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