The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted.

BACKGROUND: . Pinpointing the cells from which tumours arise is a major challenge n tumour biology. Previous work has shown that the targeted expression of a mutant ras gene within the interfollicular cell compartment of mouse skin induces the formation of benign papillomas, but these do not spontaneously progress to malignancy. We have investigated the carcinogenic effects of expressing the same oncogene in a different population of epidermal cells. RESULTS: Expression of mutant ras from a truncated keratin 5 gene promoter, which directs expression to the follicular and interfollicular cells of newborn mice and the hair follicle cells of adults, stimulated the development of acanthotic areas in newborn mice. Within one week of birth, the acanthotic skin developed areas of carcinoma in situ and adult mice developed papillomas and keratoacanthomas, the latter having a high frequency of spontaneous malignant transformation to squamous and occasionally spindle carcinomas. The benign tumours that arose had several hallmarks of tumours at a high risk of malignant progression, including suprabasal cell proliferation and heterogeneous expression of keratin 13. In contrast to tumours induced by expressing mutant ras under the control of the keratin 10 or keratin 1 gene promoters, the formation of these lesions was not dependent on wounding or a tumour promoter. CONCLUSIONS: Benign tumours that are at a risk of malignant conversion are primarily derived from cells located within the hair follicle, and the nature of the cell in which tumour initiation occurs is a major determinant of malignant potential.

The structure and evolution of parvalbumins. I. Amino acid compositional studies of parvalbumins from four perciform species.

1. Parvalbumins were isolated from the white muscle of Cynoscion regalis, Leiostomus xanthurus, and Menticirrhus americanus of the Sciaenidae and Pomatomus saltatrix of the Pomatomidae. 2. Menticirrhus contains three isoparvalbumins. The other species contain two isoparvalbumins which are designated "fast" and "slow" in accord with their electrophoretic mobilities. Measurements of the denatured molecular weights show the "slow" isoparvalbumins have slightly larger apparent molecular weights, but all apparent molecular weights are in the range 10,400-14,000. 3. Amino acid compositional studies indicate that the fast and slow isoparvalbumins in these fish represent two distinct evolutionary lineages which appear to be evolving at different rates.