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High Level Expression of the Homeobox Gene HB24 in a Human T-Cell Line Confers the Ability to Form Tumors in Nude Mice

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

² To whom requests for reprints should be addressed, at National Institutes of Health, Building 10, Room 11B-13, Bethesda, MD 20892.

The human homeobox gene HB24 is constitutively expressed in bone marrow progenitor cells and is inducible in lymphocytes. Transfection of HB24 into the T-cell line Jurkat under the control of the β-actin promoter resulted in enhanced cell growth and induction of several growth-related genes. In this study we have examined whether the presence of high levels of HB24 alters the tumorigenicity of Jurkat cells in nude mice. Subcutaneous injection of 1-2 x 10⁶ Jurkat cells or Jurkat cells transfected with a control expression vector into nude mice failed to produce tumors. However, injection of a similar number of HB24-transfected Jurkat cells resulted in local tumor formation within 4 weeks and grossly apparent metastatic lesions within 8 weeks. Histopathological analysis of tissues from the local and metastatic lesions demonstrated predominantly lymphoid cells, consistent with the morphological appearance of the injected cell line. Freshly isolated tumor cells from the nude mice incorporated similar levels of [³H]thymidine as the HB24-transfected Jurkat cells and 2-fold more than the parent Jurkat cells. Northern blot analysis of RNA prepared from the tumors revealed expression of human interleukin 2, interleukin 2 receptor -chain, HB24, and CD4. Flow cytometric analysis of the tumor cells revealed human CD4 expression but not murine CD4, confirming the human origin of the tumor cells. Media conditioned by the tumor cells contained large amounts of interleukin 2. Since natural killer cell activity is the primary immunological response against tumors in nude mice, the effects of HB24 on the responsiveness to natural killer cell-mediated cell lysis was examined. No differences in natural killer cell killing of the parent Jurkat cells and the HB24-transfected cells were observed. These data, in conjunction with recent data implicating other homeobox-containing genes in the pathogenesis of human leukemias, suggest that overexpression of HB24 in hematopoietic progenitors or T-cells may contribute to oncogenic transformation.

¹ Present address: Department of Immunology and Bacteriology, Toyama Medical and Pharmaceutical University, Toyama 930-01, Japan.

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Received 8/13/92. Accepted 10/29/92.

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