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TGF‐β1 and skin carcinogenesis: Antiproliferative effect in vitro and TGF‐β1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis
Author(s) -
Krieg Peter,
Schnapke Ruben,
Fürstenberger Gerhard,
Vogt Ingeborg,
Marks Friedrich
Publication year - 1991
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940040208
Subject(s) - keratinocyte , carcinogenesis , biology , cell culture , cancer research , hacat , epidermis (zoology) , transforming growth factor , microbiology and biotechnology , endocrinology , cancer , genetics , anatomy
The role of transforming growth factor‐β1 (TGF‐β1) in multistage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF‐β1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D (“putatively initiated” cells) responded to TGF‐β1 with slightly reduced sensitivity, and the papilloma‐producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDV C57 ) were sensitive to growth inhibition by TGF‐β1. Steady‐state levels of TGF‐β1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF‐β1 mRNA in mouse epidermis. A constitutive overexpression of TGF‐β1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.