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

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.

• Authors: Yutaka Enomoto, Kikuko Enomoto, Tadaichi Kitamura, Tadahito Kanda
• Journal: Oncogene (Oncogene) Vol. 23 Issue 29 Pg. 5014-22 (Jun 24 2004) ISSN: 0950-9232 [Print] England
• PMID: 15077167 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Keratins
• Doxycycline

Topics

• Apoptosis
• Cell Differentiation
• Cell Division
• Cell Line, Tumor
• Doxycycline (pharmacology)
• Female
• HeLa Cells
• Humans
• Keratinocytes (metabolism)
• Keratins (metabolism)
• Transfection
• Uterine Cervical Neoplasms (pathology)