Genomic organization, chromosomal localization and regulation of expression of the neuronal nuclear matrix protein NRP/B in human brain tumors

The nuclear matrix and its role in cell physiology are largely unknown, and the discovery of any matrix constituent whose expression is tissue- and/or cell-specific offers a new avenue of exploration. Studies of the novel neu ronal nuclear matrix protein, NRP/B, reveal that it is an early and highly specific marker of neuronal induction and development in vertebrates, since its expression is restricted mainly to the developing and mature nervous s ystem. These studies also show that NRP/B is involved in neuronal different iation. To further examine the structure-function of NRP/B, we have cloned and characterized the murine Nrp/b gene. The murine gene consists of four e xons interrupted by three introns that span 7.6 kb of DNA. The complete ope n reading frame is localized in exon 3, suggesting that NRP/B is highly con served during evolution. Chromosomal analysis shows that NRP/B is localized to chromosome 13 in mouse and chromosome 5q12-13 in human. Since our previous studies demonstrated that NRP/B is expressed in primary hippocampal neurons but not in primary astrocytes, we have characterized NR P/B mRNA and protein expression in various brain cell lines and in human br ain tumors. Abundant expression of NRP/B mRNA and protein was observed in h uman neuroblastoma cell lines (IMR32, SKN-MC, SKN-SH), in glioblastoma cell lines (A172, T98G, U87-MG, U118-MG, U138-MG, and U373-MG), in neuroglioma (H4) and astrocytoma cell lines (CCF-STTG1 and SW1088). Confocal analysis o f NRP/B in U87-MG glioblastoma cells indicated nuclear localization of NRP/ B. NRP/B expression was also observed in human primary brain tumors includi ng glioblastoma multiformae and astrocytomas (total of five cases). These r esults suggest that NRP/B expression is upregulated in human brain tumors i ncluding glioblastomas and astrocytomas, while under normal conditions NRP/ B expression is restricted to neurons. This study implicates a role for NRP /B in brain tumor development. (C) 2000 Elsevier Science B.V. All rights re served.