Serum factors regulate the expression of the proliferation-related genes alpha 5 integrin and keratin 1, but not keratin 10, in HaCaT keratinocytes

In the highly coordinated programme of gene expression during keratinocyte proliferation and differentiation, alpha5 integrin and keratins 1 and 10 (K 1/K10) may play important regulatory roles. We were interested in seeing wh ether, in continuously growing, immortalized HaCaT keratinocytes, similar t o normal keratinocytes, the expression of alpha5 integrin and K1/K10 was re lated to cell proliferation and differentiation. After release from cell qu iescence the expression of alpha5 integrin, both at the mRNA and protein le vels, was upregulated in the cells. At the same time, K1/K10 mRNA and prote in expression decreased dramatically, while the mRNA for D1 cyclin became d etectable, and the cells became highly proliferative. These findings indica te that alpha5 integrin and K1/K10 are involved in the regulation of HaCaT proliferation and differentiation, as in normal keratinocytes. However, HaC aT cells are different from normal keratinocytes in their ability to lose K 1/K10 expression. There is no evidence that the expression of K1/K10 can be reversed in normal keratinocytes. This ability of dedifferentiation might be a unique feature of HaCaT cells and may be a key component of their immo rtalized nature. We also found that serum factors regulate mRNA expression of alpha5 integrin and K1, but not of K10, in HaCaT cells. This information could be relevant to the understanding of normal epidermal differentiation .