CAN19 EXPRESSION IN BENIGN AND MALIGNANT HYPERPLASIAS OF THE SKIN ANDORAL-MUCOSA - EVIDENCE FOR A ROLE IN REGENERATIVE DIFFERENTIATION

CaN19, a member of the S100 family of calcium-binding proteins, is kno wn to be ''underexpressed'' in cultured breast carcinoma-derived cell lines relative to their normal counterparts, By Northern blotting, we confirm these results and find that CaN19 is also markedly ''underexpr essed'' in several carcinoma-derived cell lines of the skin, oral muco sa, and urogenital tract. However, exceptions to the inverse correlati on between CaN19 expression and malignancy have been identified, bring ing into question the hypothesis that CaN19 functions as a tumor suppr essor gene. Unexpectedly, CaN19 mRNA was strongly expressed in bulk sp ecimens of basal and squamous cell carcinomas of the skin and oral cav ity, However, in situ hybridization revealed only limited CaN19 expres sion in tumor cells themselves; the bulk of expression is localized to hyperplastic perilesional epidermis. Tumor cell. expression of CaN19 was similar in primary and locally metastatic tumors, indicating that this gene is not necessarily down-regulated during tumor progression. Coordinate overexpression of CaN19 and the ''hyperproliferative'' kera tin K6a was observed only in tissues undergoing squamous differentiati on, Taken together with other recent results from our laboratory, thes e findings suggest the hypothesis that CaN19 participates in an epider mal growth factor receptor-dependent pathway of regenerative squamous differentiation.