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Expression of c-kit Receptor in Normal and Transformed Human Nonlymphoid Tissues¹

Regina Elena Cancer Institute [P. G. N., E. S., A. B.], and Institute Biomedical Technology Consiglio Nazionale delle Ricerche [M. R. N.], Rome, Italy, and Department of Molecular Biology, Max Planck Institute für Biochemie, Martinsried, Germany [I. S., A. U.]

The protooncogene c-kit encodes a tyrosine kinase with a molecular weight of 145,000, highly related to the platelet derived growth factor/colony stimulating factor receptors. Mutations of the murine gene result in impairment of hematopoiesis, gametogenesis, and of the melanocyte cell lineage. In order to elucidate c-kit functions in development and oncogenesis we have analyzed immunohistochemically its expression in human normal and transformed nonlymphoid tissues. The receptor has been detected in spermatogonia, melanocytes, and unexpectedly, in astrocytes, renal tubules, parotid cells, thyrocytes, and breast epithelium. While the gene product is expressed in seminoma, lung tumors, and melanoma of low invasiveness, no detectable levels have been detected in thyroid and breast carcinomas, astrocytomas, and invasive melanomas. In breast tumors these findings were confirmed by paired, Northern blot analysis of RNA preparations from normal and transformed tissue. The present results demonstrate that the c-kit receptor plays a role in the development of a larger spectrum of cell lineages. Furthermore, on the basis of the transformation associated changes, we speculate that, while in some cell types, c-kit expression positively regulates mitogenesis and is selected for in neoplastic transformation, in other tissues the c-kit pathway is involved in morphogenesis and differentiation and is, therefore, negatively selected in the course of tumor progression.

¹ This work has been supported by PF ACRO, by Associazione Italiana per la Ricerca Cancro and Sugen Inc.

² To whom requests for reprints should be addressed, at Immunology Laboratory, Regina Elena Cancer Institute, Via delle Messi D'Oro, 156, 00158 Rome, Italy.

Received 3/16/92. Accepted 9/ 9/92.

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