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Induction and Autocrine Receptor Binding of Transforming Growth Factor-β2 during Terminal Differentiation of Primary Mouse Keratinocytes

Adam B. Glick^*, David Danielpour, David Morgan, Michael B. Sporn and Stuart H. Yuspa

Laboratory of Chemoprevention, and Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute Bethesda, Maryland 20892

Address requests for reprints to: Adam B. Glick, Building 41 C629, National Cancer Institute, Bethesda, Maryland 20892.

Abstract

Primary cultures of mouse keratinocytes maintain a basal cell phenotype in 0.05 mM Ca²⁺ medium, while culture in 1.4 mM Ca²⁺ results in terminal differentiation and inhibition of DNA synthesis. Induction of differentiation by Ca²⁺ results in a 10- to 20-fold increase in the expression of transforming growth factor-β2 (TGF-β2) mRNA and peptide, but a decrease in the expression of TGF-β1. In contrast, binding and cross-linking analyses show that the number of available surface 80 kilodalton (kDa) and 65 kDa TGF-β receptor types decrease during differentiation. However, a mild acid wash significantly increases the number of available receptor sites on the differentiated keratinocytes, indicating that the TGF-β receptors are unavailable for binding due to masking by endogenous ligand. A significant level of TGF-β2 secretion and receptor binding occur before the decrease in DNA synthesis, suggesting that the inhibition of DNA synthesis associated with differentiation of keratinocytes is mediated through the production and autocrine action of TGF-β2.

FOOTNOTES

^* Recipient of a National Research Service Award.

Supported by a grant from Johnson & Johnson.

Received for publication August 30, 1989. Revision received October 4, 1989. Accepted for publication October 20, 1989.

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