Activated Expression of the N- myc Gene in Human Neuroblastomas and Related Tumors

Abstract

In neuroblastoma lines in which the N-myc gene is present as a single copy, the expression of N-myc as messenger RNA is increased relative to that in nonneuroblastoma cell lines and tumors. The increase of expression in neuroblastomas with amplified N-myc genes is the result of (i) an increase in the absolute amount of expression of each N-myc gene and (ii) an increase in the copy number of the N-myc gene. A second gene--which is amplified in many of the same lines as N-myc--is expressed to about the same degree in most human cell lines and primary tumors regardless of origin (when normalized to gene copy number). Thus, a change in the regulation of N-myc expression in neuroblastomas and certain other tumors results in greatly increased expression of each N-myc gene copy.

Deubiquitinating activity of CYLD is impaired by SUMOylation in neuroblastoma cells

“…Oncogene N-MYC is often amplified in aggressive and undifferentiated neuroblastomas and its expression correlates with advanced disease. [26][27][28] Analysis of N-MYC amplification in neuroblastoma patients showed that CYLD expression was significantly lower in N-MYC-amplified compared with N-MYC-non-amplified neuroblastomas (Figure 1d). We could not find any correlation of CYLD expression with the different cellular phenotypic variants of neuroblastoma cell lines, including neuroblastic (N-type; SK-N-F1, SK-N-RA, SH-SY5Y and IMR-32) or more malignant neuroblastoma cells, the intermediate type (I-type; SK-N-BE(2)C and LA-N-2).…”

Human small-cell lung cancers show amplification and expression of the N-myc gene

“…We reported previously that eight independent human small-cell lung cancer (SCLC) lines have stable amplification and increased expression or deregulated expression alone of the c-myc gene (6,10). Recent studies have shown increased expression with or without amplification of a c-myc-related gene, N-myc, in tumors of neural origin, including neuroblastoma and retinoblastoma (7)(8)(9). In this paper, we show that six independently derived SCLC lines that express neuroendocrine properties (10)(11)(12) also have amplified Nmyc sequences and increased levels of N-myc expression compared to non-N-myc-amplified cell lines.…”

“…In the SCLC cell lines examined to date, we have found no cell lines to have the c-myc, N-myc, or L-myc genes simultaneously amplified or expressed. DISCUSSION N-myc amplification and/or expression is observed thus far in three human tumors, all of which have neural or neuroendocrine properties: neuroblastoma (7,8), retinoblastoma neuroblastoma is associated with a more advanced clinical stage (4). In neuroblastoma (7,8,30) and SCLC, the amplification is a somatic event present in tumor but not in normal tissue from the same patient.…”

“…Thus, the finding of amplification and expression of protooncogenes in tumor cells suggests an important role for the protooncogene product in the cellular and clinical biology of these tumors (3)(4)(5)(6)(7)(8)(9). We reported previously that eight independent human small-cell lung cancer (SCLC) lines have stable amplification and increased expression or deregulated expression alone of the c-myc gene (6,10).…”

Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors

“…Upon di erentiation to the mature B cell stage, coincident with completion of immunoglobulin (Ig) gene expression, N-myc expression turns o and remains o (Reth et al, 1985;Zimmerman et al, 1986;Smith et al, 1992;Morrow et al, 1992). The oncogenic potential of the human N-myc gene has been implicated in various tumors including neuroblastoma (Brodeur et al, 1984;Kohl et al, 1984), Wilms' tumor (Nisen et al, 1986), retinoblastoma (Lee et al, 1984), small cell lung carcinoma , medullary thyroid carcinoma (Roncalli et al, 1994), testis (Shuin et al, 1994), brain (Hirvonen et al, 1994), and breast (Mizukami et al, 1995). Human N-myc gene expression has been observed to be elevated in several AML and ALL leukemias and leukemic cell lines (Hirvonen et al, 1991) while not detectable in pre-preB and preB leukemic cell lines (Wetherall and Vogler, 1992).…”