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

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.

journal_name

Virology

journal_title

Virology

authors

Chen Y,Pirisi L,Creek KE

doi

10.1016/j.virol.2013.05.039

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

100-8

issue

1-2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(13)00333-4

journal_volume

444

pub_type

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