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Keratinocyte-specific POU transcription factor hSkn-1a represses the growth of cervical cancer cell lines

Oncogene volume 23, pages 5014–5022 (2004)Cite this article

Abstract

The POU transcription factor human Skn-1a (hSkn-1a) specifically promotes the proliferation of keratinocytes and enhances their differentiation. We examined the effects of hSkn-1a on cervical cancer cell lines of epithelial origin, in which the differentiation program is interrupted. From HeLa/Tet-On, a clone that can be induced to make hSkn-1a by doxycycline (HeLa/hSkn-1a) was prepared and characterized. Shortly after the induction, the cells expressed cytokeratin 10 (K10), a major marker protein in differentiating keratinocytes. While maintained for several days in the presence of doxycycline, the HeLa/hSkn-1a cells showed a slightly prolonged time of population doubling, the occasional appearance of flat cells with lowered DNA synthesis, and a low level of apoptotic DNA fragmentation. In SiHa and HeLa S3 cultures, K10 mRNA and apoptotic DNA fragmentation were detected at 48 h after infection with an adenoviral vector capable of expressing hSkn-1a. A colony inhibition assay showed that the growth of HeLa S3, SiHa, CaSki, and C-33A cells was repressed, as seen from the decreased number and average size of the drug-resistant colonies at 2 or 3 weeks after transfection with a plasmid that can express hSkn-1a and neomycin resistance gene. These results suggest that the expression of hSkn-1a represses the growth of the cervical cancer cells through the partial resumption of the differentiation pathway followed by slow suppression of cell replication and apoptosis.

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Acknowledgements

We thank Dr Kunito Yoshiike for critical reading of the paper. This work was supported by a Grant-in-Aid from the Ministry of Health and Welfare for the Second-Term Comprehensive 10-year Strategy for Cancer Control and for the Research on Human Genome and Gene Therapy, and Grant-in-Aid for Scientific Research on Priority Areas (C) from the Ministry of Education, Culture, Sports, Science, and Technology.

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Author notes

  1. Yutaka Enomoto and Kikuko Enomoto: Both these authors contributed equally to this work

Authors and Affiliations

  1. Division of Molecular Genetics, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan

    Yutaka Enomoto, Kikuko Enomoto & Tadahito Kanda

  2. Department of Urology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Tadaichi Kitamura

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  1. Yutaka Enomoto
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  2. Kikuko Enomoto
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  4. Tadahito Kanda
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Correspondence to Tadahito Kanda.

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Enomoto, Y., Enomoto, K., Kitamura, T. et al. Keratinocyte-specific POU transcription factor hSkn-1a represses the growth of cervical cancer cell lines. Oncogene 23, 5014–5022 (2004). https://doi.org/10.1038/sj.onc.1207653

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