Isolation of All <i>CD44</i> Transcripts in Human Epidermis and Regulation of Their Expression by Various Agents

<div><p>CD44, a cell surface proteoglycan, is involved in many biological events. <i>CD44</i> transcripts undergo complex alternative splicing, resulting in many functionally distinct isoforms. To date, however, the nature of these isoforms in human epidermis has not been adequately determined. In this study, we isolated all <i>CD44</i> transcripts from normal human epidermis, and studied how their expressions are regulated. By RT-PCR, we found that a number of different <i>CD44</i> transcripts were expressed in human epidermis, and we obtained all these transcripts from DNA bands in agarose and acrylamide gels by cloning. Detailed sequence analysis revealed 18 <i>CD44</i> transcripts, 3 of which were novel. Next, we examined effects of 10 different agents on the expression of <i>CD44</i> transcripts in cultured human keratinocytes, and found that several agents, particularly epidermal growth factor, hydrogen peroxide, phorbol 12-myristate 13-acetate, retinoic acid, calcium and fetal calf serum differently regulated their expressions in various patterns. Furthermore, normal and malignant keratinocytes were found to produce different <i>CD44</i> transcripts upon serum stimulation and subsequent starvation, suggesting that specific CD44 isoforms are involved in tumorigenesis via different CD44-mediated biological pathways.</p>