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Virology. 2013 Sep;444(1-2):100-8. doi: 10.1016/j.virol.2013.05.039. Epub 2013 Jun 27.

Ski protein levels increase during in vitro progression of HPV16-immortalized human keratinocytes and in cervical cancer.

Author information

1
Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.

Abstract

We compared the levels of the Ski oncoprotein, an inhibitor of transforming growth factor-beta (TGF-β) signaling, in normal human keratinocytes (HKc), HPV16 immortalized HKc (HKc/HPV16), and differentiation resistant HKc/HPV16 (HKc/DR) in the absence and presence of TGF-β. Steady-state Ski protein levels increased in HKc/HPV16 and even further in HKc/DR, compared to HKc. TGF-β treatment of HKc, HKc/HPV16, and HKc/DR dramatically decreased Ski. TGF-β-induced Ski degradation was delayed in HKc/DR. Ski and phospho-Ski protein levels are cell cycle dependent with maximal Ski expression and localization to centrosomes and mitotic spindles during G2/M. ShRNA knock down of Ski in HKc/DR inhibited cell proliferation. More intense nuclear and cytoplasmic Ski staining and altered Ski localization were found in cervical cancer samples compared to adjacent normal tissue in a cervical cancer tissue array. Overall, these studies demonstrate altered Ski protein levels, degradation and localization in HPV16-transformed human keratinocytes and in cervical cancer.

KEYWORDS:

Cervical cancer; HPV16-mediated transformation; Human keratinocytes; Human papillomavirus; Ski; TGF-beta

PMID:
23809940
PMCID:
PMC3919796
DOI:
10.1016/j.virol.2013.05.039
[Indexed for MEDLINE]
Free PMC Article
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