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Epidermal Morphogenesis and Keratin Expression in c-Ha-ras-transfected Tumorigenic Clones of the Human HaCaT Cell Line¹

Division of Differentiation and Carcinogenesis in Vitro, Institute of Biochemistry, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-6900 Heidelberg, Germany [D. B., P. B., H-J. S., N. E. F.]; Neurosciences Group, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom [C. M. R.]; Departments of Cell Biology and Dermatology, Baylor College of Medicine, Houston, Texas 77030 [D. R. R.]

Several tumorigenic (benign and malignant) clones have been raised from the human epidermal cell line HaCaT after transfection with the c-Ha-ras oncogene (val 12) (P. Boukamp et al., Cancer Res., 50: 2840–2847, 1990). In culture, these HaCaT-ras clones expressed epidermal differentiation markers, such as keratins K1 and 10, at high density or upon depletion of retinoic acid. Accordingly, as HaCaT cells, the clones formed well-differentiated stratified epithelia synthesizing K1 and 10 in surface transplants, while simple and internal epithelial keratins seen in culture were suppressed (as upon retinoic acid depletion in vitro). In transplants of HaCaT cells, in contrast to those of normal keratinocytes, K1 appeared prematurely already in basal cells, while K10 localized rather normally in the suprabasal position. Keratins 1 and 10 were also synthesized in transplants of HaCaT-ras clones (again K1 preceding K10), but both generally shifted toward upper layers. This was particularly evident in thicker transplants of malignant clones. Staining for both keratins persisted "suprabasally" in invasive tissue masses, and this corresponded to their marked expression in solid carcinomas (after s.c. injection), seen by immunofluorescence and two-dimensional gel electrophoresis. Thus, notwithstanding some variations, differentiation potential was not significantly reduced in these clones disregarding levels of ras oncogene expression and malignant properties.

¹ This work was supported in part by the US-German Collaboration Program in Cancer Research (D. B., D. R. R.) and by a FEBS Fellowship and a guest stipend of the German Cancer Research Center (C. M. R.).

² To whom requests for reprints should be addressed.

Received 3/ 7/91. Accepted 6/ 6/91.

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