Molecular characterizations of Nop16 in murine mammary tumors with varying levels of c-Myc

Abstract

NOP16, also known as HSPC111, has been identified as a MYC and estrogen regulated gene in in vitro studies, hence coexpression levels were strongly correlated. Importantly, high expression of NOP16 was associated with poor clinical outcome in breast cancer patients. However, coexpression of NOP16, MYC and estrogen receptor (ESR1) varied widely in tumors and cell lines suggesting that transcriptional regulation differed according to pathological environments. The goal of this study was to determine the expression patterns of Nop16, Myc and Esr1 in murine mammary tumors with disparate histopathological and molecular features. We hypothesized that tumor environments with relatively high Myc levels would have different coexpression patterns than tumor environments with relatively low Myc levels. We measured levels of Myc and Nop16 mRNA and protein in tumors from WAP-c-myc mice that were of high grade and metastasized frequently. In contrast, Myc and Nop16 mRNA and proteins levels were significantly lower in the less aggressive tumors that developed in NRL-TGFα mice. Tumors from both mouse lines express ESR1 protein and we found that Esr1 mRNA levels correlated positively with Myc levels in both models. However, Myc and Nop16 transcript levels correlated positively only in tumors from NRL-TGFα mice. We identified prominent NOP16 protein in nuclei and less prominent staining in the cytoplasm of luminal cells of ducts and lobules from normal mammary glands as well as in hyperplasias and tumors obtained from NRL-TGFα mice. This staining pattern was reversed in tumors from WAP-c-Myc mice as nuclear staining was faint or absent and cytoplasmic staining more pronounced. In summary, the regulation of expression and localization of NOP16 varies in tumor environments with high versus low MYC levels and demonstrate the importance of stratifying clinical breast cancers based on MYC levels.

Comprehensive nucleosome mapping of the human genome in cancer progression

“…These plots also show that nucleosome redistributions in early CRC are consistent with changes in early LAC patients for ATM, HKR1, NOP16, and KIF2B genes ( Fig. 6A-D) 29,35,38,39 . This consistency Druliner et al…”

“…Figure 3 shows five representative genes that are misregulated in adenocarcinoma: ATM, CASC1, CDKL2, CCR10, and HKR1 ( Fig. 3B-F) [29][30][31][32][33][34][35][36][37][38][39] . In each case, the locus showed substantial differences between the grade-one patient normal and tumor samples.…”

Comprehensive nucleosome mapping of the human genome in cancer progression

“…The nucleosome distribution at the ATM, HKR1, NOP16, and KIF2B genes for early LAC and all CRC patients showed that the nucleosome redistributions identified are consistent between the early CRC CRC patients, and are absent in the advanced (S4) CRC patient (Figure 6A-6D ). These plots also show that nucleosome redistributions in early CRC are consistent with changes in early LAC patients for ATM, HKR1, NOP16, and KIF2B genes (Figure 6A-6D ) [ 29 , 35 , 38 , 39 ]. This consistency between the two early adenocarcinomas is an important finding, indicating that nucleosome redistributions are a common genomic feature of early transformation.…”

Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer

“…First, we used the abovementioned LNCaP MYC overexpressing model to validate our microarray predictions and assessed transcript changes after 5 h and 12 h of MYC overexpression. As positive controls, we selected two highly ranked genes, NOP16 and DKC1, which are also previously reported MYC target genes [ 25 , 26 ], and two top up- and downregulated genes from our microarrays (RRP12 and GEMIN4 and ACPP and GPER, respectively). Strikingly, with the exception of ADSSL1 and IMPDH1, all de novo purine biosynthesis and IMP-converting enzymes showed a significant ( P < 0.05) increase in their mRNA levels upon MYC overexpression of a similar magnitude to the positive controls (Figure 1C ).…”