Keratinocyte-specific POU transcription factor hSkn-1a represses the growth of cervical cancer cell lines.
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.
Enomoto
Yutaka
Y
1Division of Molecular Genetics, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
Enomoto
Kikuko
K
Kitamura
Tadaichi
T
Kanda
Tadahito
T
D017209:Apoptosis; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
D007633:Keratins; D004318:Doxycycline