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Development of Murine Epidermal Cell Lines Which Contain an Activated ras^Ha Oncogene and Form Papillomas in Skin Grafts on Athymic Nude Mouse Hosts

Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, and ImmuQuest Laboratories, Rockville, Maryland 20850

We have developed four murine epidermal cell lines which form squamous papillomas when grafted to athymic nude mice in a reconstituted skin. Two of the lines, SP-1 and BP-4, were derived from pools of papillomas produced on SENCAR and BALB/c mouse skin, respectively, by initiation with 7,12-dimethylbenz(a)anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Line 308 was derived from BALB/c mouse skin initiated in vivo with 7,12-dimethylbenz(a)anthracene, culture of the epidermal cells, and selection of cells resistant to Ca²⁺-induced terminal differentiation. Line LC14 was derived from untreated, cultured newborn BALB/c mouse primary epidermal cells which spontaneously developed resistance to Ca²⁺-induced terminal differentiation. Each line has an activated ras^Ha gene with a mutation within codon 61. Cells from all four lines, in contrast to normal primary epidermal cells, survive in medium with Ca²⁺ levels > 0.1 mM. Clonal growth studies in culture showed a unique growth pattern for each of the four lines in medium with 1.4 mM and 0.05 mM Ca²⁺, with or without 12-O-tetradecanoylphorbol-13-acetate. Early passage cells of these lines should provide a valuable resource for detecting genes or genetic alterations which complement an activated ras gene to cause malignant conversion and for studying the biology of tumor promotion.

¹ To whom requests for reprints should be addressed, at Room 3B25, Building 37, NIH, Bethesda, MD 20892.

² Supported by the United States-Poland Scientific Exchange Program.

Received 6/24/87. Revised 9/22/87. Accepted 10/ 7/87.

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