INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes

  • Authors:
    • Sabine Hombach-Klonisch
    • Cuong Hoang-Vu
    • Astrid Kehlen
    • Raoul Hinze
    • Hans-Jürgen Holzhausen
    • Ekkehard Weber
    • Bernd Fischer
    • Henning Dralle
    • Thomas Klonisch
  • View Affiliations

  • Published online on: May 1, 2003     https://doi.org/10.3892/ijo.22.5.993
  • Pages: 993-1001
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Abstract

The insulin-like hormone INSL-3, also named relaxin-like factor (RLF) or Leydig-derived insulin-like peptide (LEY-IL), is expressed in various reproductive tissues and is regarded a marker of differentiation in human testicular Leydig cells. Recently, we have identified differential expression of human INSL-3 in neoplastic Leydig cells and mammary epithelial cells suggesting an involvement of INSL-3 in tumor biology. Here we have investigated the expression of INSL-3 in human thyroid carcinoma cell lines and in the human thyroid gland which has been shown to express transcripts for the G protein coupled INSL-3 receptor LGR8. When we determined the expression of INSL-3 in eight human thyroid carcinoma cell lines, a novel INSL-3 splice variant containing a 95 bp out-of-frame insertion at the beginning of exon II of the INSL-3 gene was discovered. Treatment of the human anaplastic thyroid carcinoma cell line 8505C with diethylstilbestrol (DES) caused a significant dose-dependent transcriptional down-regulation of INSL-3 and a marked up-regulation of LGR8. Employing in situ hybridization to detect INSL-3 transcripts and specific rabbit antisera against the INSL-3 proteins, both INSL-3 isoforms were detected in patients with Graves' disease (n=10), follicular carcinomas (FTC; n=12), papillary carcinomas (PTC; n=9) and undifferentiated anaplastic carcinomas (UTC; n=15). By contrast, thyrocytes of all 15 benign goiter tissues studied were devoid of both INSL-3 isoforms, mRNA and protein. Our data indicate that INSL-3 hormone is up-regulated in hyperplastic and neoplastic human thyrocytes suggesting that the INSL-3 isoforms may serve as additional markers for hyperplastic and neoplastic human thyrocytes. In the anaplastic thyroid carcinoma cell line 8505C, the regulation of both INSL-3 and LGR8 by estrogen may be the first indication of a novel hormonally responsive, auto-/paracrine INSL-3 LGR8 ligand receptor system active in human thyroid carcinoma cells.

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May 2003
Volume 22 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hombach-Klonisch S, Hoang-Vu C, Kehlen A, Hinze R, Holzhausen H, Weber E, Fischer B, Dralle H and Klonisch T: INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes. Int J Oncol 22: 993-1001, 2003
APA
Hombach-Klonisch, S., Hoang-Vu, C., Kehlen, A., Hinze, R., Holzhausen, H., Weber, E. ... Klonisch, T. (2003). INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes. International Journal of Oncology, 22, 993-1001. https://doi.org/10.3892/ijo.22.5.993
MLA
Hombach-Klonisch, S., Hoang-Vu, C., Kehlen, A., Hinze, R., Holzhausen, H., Weber, E., Fischer, B., Dralle, H., Klonisch, T."INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes". International Journal of Oncology 22.5 (2003): 993-1001.
Chicago
Hombach-Klonisch, S., Hoang-Vu, C., Kehlen, A., Hinze, R., Holzhausen, H., Weber, E., Fischer, B., Dralle, H., Klonisch, T."INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes". International Journal of Oncology 22, no. 5 (2003): 993-1001. https://doi.org/10.3892/ijo.22.5.993