Contributed equally to the work.
Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis
Article first published online: 2 JUN 2011
© 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology
International Journal of Andrology
Volume 34, Issue 4pt2, pages e160–e174, August 2011
How to Cite
Gillis, A. J. M., Stoop, H., Biermann, K., van Gurp, R. J. H. L. M., Swartzman, E., Cribbes, S., Ferlinz, A., Shannon, M., Oosterhuis, J.W. and Looijenga, L. H. J. (2011), Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis. International Journal of Andrology, 34: e160–e174. doi: 10.1111/j.1365-2605.2011.01148.x
- Issue published online: 26 JUL 2011
- Article first published online: 2 JUN 2011
- Received 29 November 2010; revised 5 January 2011; accepted 7 January 2011
- differentiation regulation;
- germ cells;
- germ-cell tumours;
- TaqMan protein assays
OCT3/4, NANOG, SOX2 and, most recently, LIN28 have been identified as key regulators of pluripotency in mammalian embryonic and induced stem cells, and are proven to be crucial for generation of the mouse germ-cell lineage. These factors are a hallmark of certain histological types of germ-cell tumours (GCTs). Here, we report novel information on the temporal and spatial expression pattern of LIN28 during normal human male germ-cell development as well as various types of GCTs. To investigate LIN28 expression, immunohistochemical analyses and quantitative proximity ligation assay-based TaqMan protein assays were applied on snap-frozen and formalin-fixed, paraffin-embedded samples as well as representative cell lines. LIN28 was found in primordial germ cells, gonocytes and pre-spermatogonia, in contrast to OCT3/4 and NANOG, which were found only in the first two stages. LIN28 was also found in all precursor lesions (carcinoma in situ and gonadoblastoma) of type II GCTs, as well as the invasive components seminoma and the non-seminomatous elements embryonal carcinoma and yolk sac tumour. Choriocarcinoma showed a heterogeneous pattern, while teratomas and spermatocytic seminomas (type III GCTs) were negative. This expression pattern suggests that LIN28 is associated with malignant behaviour of type II GCTs. Cell line experiments involving siRNA knockdown of LIN28, OCT3/4 and SOX2 showed that LIN28 plays a role in the maintenance of the undifferentiated state of both seminoma and embryonal carcinoma, closely linked to, and likely upstream of OCT3/4 and NANOG. In conclusion, LIN28 regulates the differentiation status of seminoma and embryonal carcinoma and is likely to play a related role in normal human germ-cell development.