Transforming Growth Factor-β Up-Regulates the Expression of the Genes for β4 Integrin and Bullous Pemphigoid Antigens (BPAG1 and BPAG2) in Normal and Transformed Human Keratinocytes

ABSTRACT cdc25A is a tyrosine phosphatase that activates G1cyclin-dependent kinases (Cdk’s). In human keratinocytes,cdc25A expression is down-regulated after the initial drop in Cdk activity caused by cell exposure to the antimitogenic cytokine transforming growth factor β (TGF-β) or removal of serum factors. Here we show that the TGF-β-inhibitory-response element in thecdc25A promoter maps to an E2F site at nucleotides −62 to −55 from the transcription start site. This site is not required for basal transcription in keratinocytes. We provide evidence that the cell cycle arrest program activated by TGF-β in human keratinocytes includes the generation of E2F4-p130 complexes that in association with histone deacetylase HDAC1 inhibit the activity of thecdc25A promoter from this repressor E2F site. This mechanism is part of a program that places keratinocytes in the quiescent state following the initial drop in Cdk activity caused by cell exposure to TGF-β.

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Altered regulation of intercellular communication by epidermal growth factor, transforming growth factor-β and peptide hormones in normal human keratinocytes

Carcinogenesis ◽

10.1093/carcin/10.1.13 ◽

1989 ◽

Vol 10 (1) ◽

pp. 13-20 ◽

Cited By ~ 58

Author(s):

B.V. Madhukar ◽

S.Y. Oh ◽

C.C. Chang ◽

M. Wade ◽

J.E. Trosko

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Intercellular Communication ◽

Transforming Growth Factor ◽

Human Keratinocytes ◽

Transforming Growth Factor Β ◽

Normal Human Keratinocytes ◽

Normal Human ◽

Epidermal Growth ◽

Altered Regulation

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Glycosylphosphatidylinositol-anchored Proteins Regulate Transforming Growth Factor-β Signaling in Human Keratinocytes

Journal of Biological Chemistry ◽

10.1074/jbc.m308492200 ◽

2003 ◽

Vol 278 (49) ◽

pp. 49610-49617 ◽

Cited By ~ 18

Author(s):

Betty Yuet Ye Tam ◽

Kenneth W. Finnson ◽

Anie Philip

Keyword(s):

Growth Factor ◽

Transforming Growth Factor ◽

Human Keratinocytes ◽

Transforming Growth Factor Β

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S100A11, an Dual Mediator for Growth Regulation of Human Keratinocytes

Molecular Biology of the Cell ◽

10.1091/mbc.e07-07-0682 ◽

2008 ◽

Vol 19 (1) ◽

pp. 78-85 ◽

Cited By ~ 49

Author(s):

Masakiyo Sakaguchi ◽

Hiroyuki Sonegawa ◽

Hitoshi Murata ◽

Midori Kitazoe ◽

Jun-ichiro Futami ◽

...

Keyword(s):

Growth Factor ◽

Growth Regulation ◽

Transforming Growth Factor ◽

Human Keratinocytes ◽

Transforming Growth Factor Β ◽

Growth Stimulation ◽

Nuclear Factor Κb ◽

Camp Response Element Binding ◽

Element Binding Protein ◽

Squamous Cancer

We previously revealed a novel signal pathway involving S100A11 for inhibition of the growth of normal human keratinocytes (NHK) caused by high Ca++ or transforming growth factor β. Exposure to either agent resulted in transfer of S100A11 to nuclei, where it induced p21WAF1. In contrast, S100A11 has been shown to be overexpressed in many human cancers. To address this apparent discrepancy, we analyzed possible new functions of S100A11, and we provide herein evidence that 1) S100A11 is actively secreted by NHK; 2) extracellular S100A11 acts on NHK to enhance the production of epidermal growth factor family proteins, resulting in growth stimulation; 3) receptor for advanced glycation end products, nuclear factor-κB, Akt, and cAMP response element-binding protein are involved in the S100A11-triggered signal transduction; and 4) production and secretion of S100A11 are markedly enhanced in human squamous cancer cells. These findings indicate that S100A11 plays a dual role in growth regulation of epithelial cells.

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