PCNA levels in neuroblastoma are increased in tumors with an amplified N- myc gene and in metastatic stage tumors

N- myc oncogene amplification in neuroblastoma has been found to be significantly associated with advanced stage disease and tumor progression. However, there is a lack of data on tumors, regarding the relationship between N- myc gene amplification and proliferation activity. Proliferating cell nuclear antigen (PCNA) is a proliferation-induced 36 kD nuclear protein that is the auxiliary component of DNA polymerase δ. PCNA levels in tissues have been found to correlate with proliferative activity. We have examined PCNA levels in neuroblastomas in relation to N- myc gene amplification and tumor stage. Statistically, significantly higher levels of PCNA were observed in tumors with an amplified N- myc gene relative to tumors with a single gene copy. The highest levels of PCNA were observed in advanced stage tumors with an amplified N- myc gene. Treatment of neuroblastoma cells in culture with retinoic acid, which induces differentiation, resulted in a substantial decrease in PCNA. Our results suggest that PCNA levels may reflect differences in proliferative activity between neuroblastomas, related to stage of the disease and to N- myc gene copy number.[/p ]Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42581/1/10585_2004_Article_BF00880069.pd

Oncogene and Growth Factor Expression in MEN 2 and Related Tumors

Pheochromocytomas occur sporadically or in individuals affected by inherited syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B, neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and familial MTC. Little is known of the molecular genetic background of these tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras oncogenes does not occur in these tumors, but that deletions of the short arm of chromosome 1 are extremely common (\u3e 60%) and may indicate loss of a suppressor gene in the chromosomal region 1p31-36. We have examined the structure and expression of N-myc, c-myc, L-myc, c-mos, nerve growth factor (β-NGF), and the low affinity nerve growth factor receptor (LNGFR) in a series of pheochromocytomas and MTCs from patients with hereditary and sporadic diseases. Southern analysis, using radiolabeled DNA probes, revealed no evidence of amplification or rearrangement of these genes in any normal or tumor tissues except for loss of heterozygosity at the L-myc locus (1p32) in 9 pheochromocytomas from patients with MEN 2A or MEN 2B, in 5 of 11 non-MEN pheochromocytomas, and in 3 of 24 non-MEN MTCs. Gene expression at the RNA level was examined by Northern analysis or ribonuclease protection assay (RPA) using radiolabeled DNA or cRNA probes. C-myc transcripts were detectable at low levels in all tumors tested. L-myc and c-mos transcripts were not detectable \u27in any tumor, and N-myc transcripts were detectable at low levels in all tumors by Northern analysis or RPA. LNGFR transcripts were not detectable in four tumors (two vHL pheochromocytomas, two sporadic pheochromocytomas), but were present at low levels in all other tumors. High levels of gene transcripts, or abnormally sized transcripts, were not seen in any tumor. Deletion of chromosome 1p remains the most consistent and significant molecular genetic abnormality yet identified in these tumors