Increase in alkaline phosphodiesterase I activity of tumor-derived cultured fibroblasts from neurofibromatosis patients

Abstract

Neurofibromatosis (NFl) is a common autosomal dominant disorder involving the central and peripheral nervous systems and is characterized by cutaneous tumors. The NFI gene was recently cloned and its gene product is GTPaseactivating protein (GAP), which regulates the signaling function of P2lras in differentiation and proliferation [l-3]. Recently Menon et al. reported that the normal allele of NFl gene is not mutated in most benign neurofibromas [4]. Hence other gene products need to be explored in the tumors. However, no consistent biochemical abnormality has been found in tissues affected by NFl. In an effort to elucidate the pathogenesis of NFl, we have been searching for chemical differences between three types of cells: tumor-derived and normal-appearing Iibroblasts from NFl patients and control tibroblasts. In this study we found that the activity of membrane-bound alkaline phosphodiesterase I (EC 3.1.4.1) is increased significantly in tumor-derived fibroblasts while the activity of 5’-nucleotidase, a membrane marker enzyme, is not. Furthermore alkaline phosphodiesterase I is induced due to nicotinamide at the transcriptional level in tumor-derived cells [5]. Cells from NFl