Transforming Growth Factor-1 Inhibits Nucleosomal Fragmentation in Human Keratinocytes following Loss of Adhesion

doi:10.1074/jbc.271.1.5

Transforming Growth Factor-1 Inhibits Nucleosomal Fragmentation in Human Keratinocytes following Loss of Adhesion (*)

From the Department of Pathology and the Environmental Toxicology Center, Madison, Wisconsin 53706

^§ To whom correspondence should be addressed:
Dept. of Pathology and the Environmental Toxicology Center, 5638 Medical Sciences Center, Madison, WI 53706.
Tel.: 608-262-2884; Fax: 608-265-3301; blallenh{at}facstaff.wisc.edu.

Abstract

We have investigated the role of transforming growth factor-β1 (TGF-β1) in suspension-induced programmed cell death of cultured human keratinocytes. Suspension of keratinocytes in semisolid medium induces TGF-β1 mRNA levels and synthesis of bioactive TGF-β1 protein. Concomitant with the suspension-induced increase in secreted TGF-β1 levels, steady state mRNA levels for c-myc are decreased. Both exogenously added and endogenously produced TGF-β1 attenuate suspension-induced nucleosomal fragmentation in keratinocytes. We propose that TGF-β1 may function to protect keratinocytes from DNA fragmentation following loss of cell-substratum and/or cell-cell contact. Taken together, our findings suggest that loss of cell-substratum and/or cell-cell adhesion is an important component of an apoptotic signal transduction cascade regulated by TGF-β1 in normal human stratified squamous epithelia.

Footnotes

↵* These studies were supported in part by National Institutes of Health Grant AR40284 (to B. L. A.-H.), National Institute of Environmental Health Science Traineeship T32 ES07015 (to K. F. S.), and Predoctoral Individual National Research Service Award F31 AR08366 (to K. F. S.). This is contribution 276 from the Environmental Toxicology Center, University of Wisconsin. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹K. F. Sachsenmeier and B. L. Allen-Hoffmann, submitted for publication.
↵² The abbreviations used are:

TGF-β1

transforming growth factor β1

DMEM

Dulbecco's modified Eagle's medium

EGF

epidermal growth factor

NRK

normal rat kidney

ddATP

dideoxy-ATP.
- Received September 14, 1995.
- Revision received October 25, 1995.