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High trefoil factor 1 (TFF1) expression in human retinoblastoma cells correlates with low growth kinetics, increased cyclin-dependent kinase (CDK) inhibitor levels and a selective down-regulation of CDK6

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Abstract

Trefoil factor family (TFFs) peptides facilitate epithelial restitution, but also effect cell proliferation and apoptosis of normal and various cancer cell lines. In a recent study by our group, TFF2 expression was demonstrated in the murine retina, where it exhibits pro-proliferative and pro-apoptotic effects. In the present study, we investigated the expression and function of TFF peptides in eight human retinoblastoma cell lines. TFF1 was the only TFF peptide expressed at detectable levels in immunoblots of retinoblastoma cells. TFF1 expression levels were highly variable in different retinoblastoma cell lines and negatively correlated with cell growth curves. Recombinant human TFF1 had a negative effect on cell viability and caused a reduction in cell proliferation. Retinoblastoma cell lines with high TFF1 expression levels exhibited a selective down-regulation of cyclin-dependent kinase (CDK) 6, whereas CDK4 and CDK2 seem to be unaffected by TFF1 expression. In immunocytochemical studies, we observed a nuclear co-localization of TFF1 and CDK2 in Cajal bodies (CBs). In high TFF1 expressing human retinoblastoma cell lines CBs were smaller and higher in number compared to retinoblastoma lines with low TFF1 expression, indicating differences in cell cycle status between the different retinoblastoma cell lines. Our data further support the notion for a potential tumor suppressor function of TFF1. The nuclear localization of TFF1 in CBs—considered to play a role in cell cycle progression, potentially acting as a platform for CDK-cyclin function—offers a new impetus in the ongoing search for potential TFF1 interacting proteins.

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Acknowledgments

We thank U. Gerster and U. Laub for excellent technical assistance, H. Stephan for generously providing the different retinoblastoma cell lines and E. Cario for providing human duodenum and stomach tissue samples. We also would like to thank A. Hecht for the pCS2+ expression vector and the HEK293 cells and D. Gioè and C. Philippeit for proofreading of the manuscript.

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  1. Department of Neuroanatomy, Medical Faculty, Institute of Anatomy, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Andreas Weise & Nicole Dünker

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  1. Andreas Weise
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  2. Nicole Dünker
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Correspondence to Nicole Dünker.

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Weise, A., Dünker, N. High trefoil factor 1 (TFF1) expression in human retinoblastoma cells correlates with low growth kinetics, increased cyclin-dependent kinase (CDK) inhibitor levels and a selective down-regulation of CDK6. Histochem Cell Biol 139, 323–338 (2013). https://doi.org/10.1007/s00418-012-1028-y

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