TGF-β regulation of gene expression at early and late stages of HPV16-mediated transformation of human keratinocytes.

Abstract:

:In our in vitro model for HPV16-mediated transformation, HPV16-immortalized human keratinocytes (HKc/HPV16) give rise to differentiation resistant, premalignant cells (HKc/DR). HKc/DR, but not HKc/HPV16, are resistant to growth inhibition by transforming growth factor beta (TGF-β), due to a partial loss of TGF-β receptor type I. We show that TGF-β activates a Smad-responsive reporter construct in HKc/DR to about 50% of the maximum levels of activation observed in HKc/HPV16. To investigate the functional significance of residual TGF-β signaling in HKc/DR, we compared gene expression profiles elicited by TGF-β treatment of HKc/HPV16 and HKc/DR on Agilent 44k human whole genome microarrays. TGF-β altered the expression of cell cycle and MAP kinase pathway genes in HKc/HPV16, but not in HKc/DR. However, epithelial-mesenchymal transition (EMT) responses to TGF-β were comparable in HKc/HPV16 and HKc/DR, indicating that the signaling pathways through which TGF-β elicits growth inhibition diverge from those that induce EMT in HPV16-transformed cells.

journal_name

Virology

journal_title

Virology

authors

Kowli S,Velidandla R,Creek KE,Pirisi L

doi

10.1016/j.virol.2013.08.034

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

63-73

issue

1-2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(13)00507-2

journal_volume

447

pub_type

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