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The effect of differentiation on the expression of multidrug resistance proteins in murine keratinocytes

Multidrug resistance (MDR) proteins are best characterized by their role in expelling conventional chemotherapeutic agents from cancer cells, thus preventing cell dealth. In nonpathogenic states, MDRs, ATP‐binding cassette transporters, efflux xenotoxins from cells. Expression of MDRs is likely to be crucial to normal functioning of keratinocytes of the epidermis, which are constantly bombarded by environmental agents. MDRs have previously been shown to be expressed in keratinocytes with greatest levels of MDRs found in the basal layer of the epidermis, presumably to preserve epidermal stem cells. To determine the effect of differentiation on the expression of MDRs in keratinocytes, we have cultured primary keratinocytes from Balb/C neonatal mice, induced differentiation by calcium, and compared expression levels of MDRs throughout the process of keratinocyte differentiation. P‐gp and MRP1, but not MRP2 mRNAs were detected in both neonatal epidermis and primary keratinocytes. Addition of calcium to primary keratinocyte cultures lead to induction of differentiation, as determined by keratin 1 expression. Preliminary data indicate a down‐regulation of P‐gp and MRP1 at both the mRNA and protein level in response to differentiation. An understanding of the mechanisms by which MDR expression is down‐regulated in nonpathogenic states could aid in the design of more successful cancer therapies.