Summary
A tight association between the expression of the protooncogene c-myc and the proliferation of trophoblast in first trimester human placentae has been reported, supporting the view that c-myc is under close control of the cell cycle. However, this has not been verified in several other cells systems. Therefore we reexamined the exact localization of myc expression at the transcriptional and translational level in 20 first trimester and three term placentae. Myc mRNA and protein was sparse or absent at term but abundant in early gestation placentae. The proliferative cell columns and the villous cytotrophoblast contained the greatest amounts, revealing myc protein in around 60–70% of villous cytotrophoblast cells. Unexpectedly, a considerable fraction of the syncytiotrophoblast nuclei of early placentae (20%) also showed myc expression, and this was particularly evident on the protein level. The myc content estimated by immunohistochemistry decreased with increasing placental maturation. In addition, prominent myc expression was seen in decidual cells, suggesting a paracrine growth regulation of the gestational endometrium.
Our findings do not support the notion that myc expression is closely cell cycle-dependent. On the contrary, it appears that in the human placenta, myc expression characterizes the phase of rapid organ development in the first trimester and is not restricted to the proliferative cytotrophoblast.
Similar content being viewed by others
References
Adamson ED (1987) Expression of protooncogenes in the placenta. Placenta 8:449–466
Alitalo K, Schwab M, Lin CC, Varmus HE, Bishop JM (1983) Homogenously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci USA 80:1707–1711
Arnholdt H, Löhrs U (1989) Proliferation and differentiation of Langhans’ cells. Placenta 10:458
Arnholdt H, Meisel F, Fandrey K, Löhrs U Proliferation of villous trophoblast of human placenta in normal and abnormal pregnancies. Virchows Arch [B] 60:365–372
Cantle SJ, Kaufmann P, Luckhardt M, Schweikhart G (1987) Interpretation of syncytial sprouts and bridges in the human placenta. Placenta 8:221–234
Chegini N, Rao CV (1985) Epidermal growth factor binding to human amnion, chorion, decidua, and placenta from mid- and term pregnancy: quantitative light microscopic autoradiographic studies. J Clin Endocrinol Metabol 61:529–535
Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, Mac-Donald S, Pulford KAF, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229
Dalla Favera R, Gelmann EP, Martinotti S, Franchini G, Papas TS, Gallo RC, Wong-Staal F (1982) Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC 29). Proc Natl Acad Sci USA 79:6497–6501
Dani C, Blanchard JM, Piechaczyk M, El Sabouty S, Marty L, Jeanteur P (1984) Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci USA 81:7046–7050
Dotto GP, Gilman MZ, Maruyama M, Weinberg RA (1986) C-myc and c-fos expression in differentiating mouse primary keratinocytes. EMBO J 5:2853–2857
Evan GI, Lewis GK, Ramsay G, Bishop JM (1985) Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol 5:3610–3616
Goustin AS, Betsholtz C, Pfeifer-Ohlsson S, Persson H, Rydnert J, Bywater M, Holmgren G, Heldin C-H, Westermark B, Ohlsson R (1985) Coexpression of the sis and myc proto-oncogenes in developing human placenta suggests autocrine control of trophoblast growth. Cell 41:301–312
Hall PA, Stearn PM, Butler MG, Ardenne AJD (1987) Acetone/periodate-lysine-paraformaldehyde (PLP) fixation and improved morphology of cryostat sections for immunohistochemistry. Histopathol 11:93–101
Han VKM, Hunter ES, Pratt RM, Zendegui JG, Lee DC (1987) Expression of rat transforming growth factor alpha mRNA during development occurs predominantly in the maternal decidua. Mol Cell Biol 7:2335–2343
Hann SR, Eisenmann RN (1984) Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol 4:2486–2497
Hann SR, Thompson CB, Eisenman RN (1985) C-myc oncogene protein synthesis is independent of the cell cycle in human and avian cells. Nature 314:366–369
Heikkila R, Schwab G, Wickstrom E, Loke SL, Pluznik DH, Watt R, Neckers LM (1987) A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1. Nature 328:445–449
Jack AS, Kerr IB, Evan G, Lee FD (1986) The distribution of the c-myc oncogene product in malignant lymphomas and various normal tissues as demonstrated by immunocytochemistry. Br J Cancer 53:713–719
Kaufmann (1972) Untersuchungen über die Langhanszellen in der menschlichen Plazenta. Z Zellforsch 128:283–302
Klimpfinger M, Zisser G, Ruhri C, Pütz B, Steindorfer U, Höfler H (1990) Expression of c-myc and c-fos mRNA in colorectal carinoma in man. Virchows Arch [B] 59:165–171
Larsson L-G, Gray HE, Tötterman T, Pettersson U, Nilsson K (1987) Drastically increased expression of myc and fos protooncogenes during in vitro differentiation of chronic lymphocytic leukemia cells. Proc Natl Acad Sci USA 84:223–227
Lawrence JB, Singer RH (1986) Intracellular localization of messenger RNAs for cytoskeletal proteins. Cell 45:407–415
Manuelidis L, Langer-Safer PR, Ward DC (1982) High-resolution mapping of satellite DNA using biotin-labeled DNA probes. J Cell Biol 95:619–625
Maruo T, Mochizuki M (1987) Immunohistochemical localization of epidermal growth factor receptor and myc oncogene product in human placenta: implication for trophoblast proliferation and differentiation. Am J Obstet Gynecol 156:721–727
Matsumura T, Dohi K, Takanashi A, Ito H, Tahara E (1990) Alteration and enhanced expression of the c-myc oncogene in human colorectal carcinomas. Pathol Res Pract 186:205–211
Moelling K (1986) Properties of the myc and myb gene products. In: Kahn P, Graf T (eds) Oncogenes and growth control. Springer, Berlin Heidelberg New York Tokyo, pp 271–277
Niedobitek G, Finn T, Herbst H, Stein H (1989) In situ hybridization using biotinylated probes. An evaluation of different detection systems. Pathol Res Pract 184:343–348
Pfeifer-Ohlsson S, Goustin AS, Rydnert J, Wahlström T, Bjersing L, Stehelin D, Ohlsson R (1984) Spatial and temporal pattern of cellular myc oncogene expression in developing human placenta: implications for embryonic cell proliferation. Cell 38:585–596
Pfeifer-Ohlsson S, Rydnert J, Goustin AS, Larsson E, Betsholtz C, Ohlsson R (1985) Cell-type-specific pattern of myc protooncogene expression in developing human embryos. Proc Natl Acad Sci USA 82:5050–5054
Polacarz SV, Hey NA, Stephenson TJ, Hill AS (1989) C-myc oncogene product P62c-myc in ovarian mucinous neoplasms: immunohistochemical study correlated with malignancy. J Clin Pathol 42:148–152
Pollard JW, Bartocci A, Arceci R, Orlofsky A, Ladner MB, Stanley ER (1987) Apparent role of the macrophage growth factor, CSF-1, in placental development. Nature 330:484–486
Rigby PW, Dieckmann M, Rhodes C, Berg P (1977) Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol 113:237–251
Roux P, Blanchard JM, Fernandez A, Lamb N, Jeanteur P, Piechaczyk M (1990) Nuclear localization of c-fos, but not v-fos proteins, is controlled by extracellular signals. Cell 63:341–351
Sachs L (1988) Statistische Methoden—Planung und Auswertung. Springer, Berlin Heidelberg New York Tokyo, pp 39–40
Schmid P, Schulz WA, Hameister H (1989) Dynamic expression pattern of the myc protooncogene in midgestation mouse embryos. Science 243:226–229
Sikora K, Evan G, Stewart J, Watson JV (1985) Detection of the c-myc oncogene product in testicular cancer. Br J Cancer 52:171–176
Sporn MB, Todaro GJ (1980) Autocrine secretion and malignant transformation of cells. N Engl J Med 303:378–380
Stewart J, Evan G, Watson J, Sikora K (1986) Detection of the c-myc oncogene product in colonic polyps and carcinomas. Br J Cancer 53:1–6
Studzinski GP, Brelvi ZS, Feldman SC, Watt RA (1986) Participation of c-myc protein in DNA synthesis of human cells. Science 234:467–470
Ten Kate J, Eidelman S, Bosman FT, Damjanov I (1989) Expression of c-myc protooncogene in normal human intestinal epithelium. J Histochem Cytochem 37:541–545
Thompson CB, Challoner PB, Neiman PE, Groudine M (1985) Levels of c-myc oncogene mRNA are invariant throughout the cell cycle. Nature 314:363–366
Author information
Authors and Affiliations
Additional information
Supported by a grant of the Deutsche Forschungsgemeinschaft (SFB 232) to H.A. and U.L.
Rights and permissions
About this article
Cite this article
Diebold, J., Arnholdt, H., Lai, M.D. et al. C-myc expression in early human placenta —a critical evaluation of its localization. Virchows Archiv B Cell Pathol 61, 65–73 (1992). https://doi.org/10.1007/BF02890406
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02890406