The restricted expression pattern of the Hodgkin's lymphoma-associated cytokine receptor CD30 is regulated by a minimal promoter

One of the most peculiar immunohistological characteristics of the tumour c ells of Hodgkin's lymphoma, anaplastic large cell lymphoma (ALCL), and embr yonal carcinoma of the testis is the expression of the CD30 antigen. Physio logically, CD30 expression is restricted to a few activated lymphocytes in normal lymphoid tissue and a small population of decidual cells. To clarify the reasons behind this highly restricted expression pattern and to learn about the combination of transcription factors involved in this regulation in Hodgkin's lymphoma and other CD30(+) malignancies, the 5'-flanking regul atory region of the cd30 gene was analysed. The major transcription start s ite was determined to be 270 bases upstream of the translational start codo n in the Hodgkin's lymphoma-derived cell lines L591 and L428, Reporter gene assays revealed that the CD30 promoter (-413 to 84) induces a 50- to 1000- fold higher luciferase expression in CD30(+) human lymphoid cell lines (Co, Jurkat, and the Hodgkin's lymphoma-derived cell line L540) than in CD30(-) human lymphoid cell lines (DG75, SUP-T1, and U698M), CD30- human carcinoma cell lines (HeLa and MCF-7), or COS1 cells. Deletion analysis defined a TA TA-less, minimal promoter sequence from -164 to 84, The transcription facto r Sp1 and members of the Ets family induce CD30 expression, whereas the tra nscription factor Sp3 diminishes its induction. These data suggest that a h igh Sp1/Sp3 expression ratio and a peculiar expression pattern of the Ets t ranscription factors are involved in the overexpression of CD30 and might c ontribute to the transformation of CD30+ tumour cells. Copyright (C) 2000 J ohn Wiley & Sons, Ltd.