scholarly journals Multiple mechanisms for transcriptional regulation of the myc gene family in small-cell lung cancer.

1988 ◽  
Vol 8 (8) ◽  
pp. 3373-3381 ◽  
Author(s):  
G Krystal ◽  
M Birrer ◽  
J Way ◽  
M Nau ◽  
E Sausville ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Gene Family ◽  
Gene Amplification ◽  
Cell Lung Cancer ◽  
Promoter Activity ◽  
Small Cell ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Myc Gene

The molecular mechanisms reported to regulate the expression of myc family genes are multiple and complex and include gene amplification, transcriptional activation, transcriptional attenuation, and mRNA stability. We have investigated which of these mechanisms are responsible for the extreme variation in myc gene family mRNA levels observed in human small-cell lung cancer cell lines. In addition to gene amplification, a block to nascent mRNA chain elongation, causing attenuation of transcription, is an important regulatory mechanism controlling the steady-state levels of c-myc and L-myc mRNA. The loss of transcriptional attenuation is correlated with overexpression of these two genes in cell lines which do not show gene amplification. Expression of c-myc mRNA appears to be dependent on promoter activity and attenuator function. In contrast, regulation of expression of the N-myc gene does not involve transcriptional attenuation; steady-state mRNA levels are correlated with promoter activity as well as gene amplification. We conclude that transcriptional regulation of each member of the myc gene family is accomplished by a different assortment of complex mechanisms, including gene copy number, promoter activation, and transcriptional attenuation. Interference at multiple points in this complex regulatory process appears to be an important mechanism by which small-cell lung cancer and other human tumors evade growth control.

Multiple mechanisms for transcriptional regulation of the myc gene family in small-cell lung cancer

1988 ◽  
Vol 8 (8) ◽  
pp. 3373-3381
Author(s):  
G Krystal ◽  
M Birrer ◽  
J Way ◽  
M Nau ◽  
E Sausville ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Gene Family ◽  
Gene Amplification ◽  
Cell Lung Cancer ◽  
Promoter Activity ◽  
Small Cell ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Myc Gene

The molecular mechanisms reported to regulate the expression of myc family genes are multiple and complex and include gene amplification, transcriptional activation, transcriptional attenuation, and mRNA stability. We have investigated which of these mechanisms are responsible for the extreme variation in myc gene family mRNA levels observed in human small-cell lung cancer cell lines. In addition to gene amplification, a block to nascent mRNA chain elongation, causing attenuation of transcription, is an important regulatory mechanism controlling the steady-state levels of c-myc and L-myc mRNA. The loss of transcriptional attenuation is correlated with overexpression of these two genes in cell lines which do not show gene amplification. Expression of c-myc mRNA appears to be dependent on promoter activity and attenuator function. In contrast, regulation of expression of the N-myc gene does not involve transcriptional attenuation; steady-state mRNA levels are correlated with promoter activity as well as gene amplification. We conclude that transcriptional regulation of each member of the myc gene family is accomplished by a different assortment of complex mechanisms, including gene copy number, promoter activation, and transcriptional attenuation. Interference at multiple points in this complex regulatory process appears to be an important mechanism by which small-cell lung cancer and other human tumors evade growth control.

scholarly journals The 5′-flanking region of humanCD24 gene has cell-type-specific promoter activity in small-cell lung cancer

1998 ◽  
Vol 78 (4) ◽  
pp. 496-502 ◽  
Author(s):  
Maria K. Pass ◽  
Gianluca Quintini ◽  
Jürg A. Zarn ◽  
Sandra M. Zimmermann ◽  
Jürg A. Sigrist ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Promoter Activity ◽  
Small Cell ◽  
Cell Type ◽  
Small Cell Lung ◽  
Cell Type Specific ◽  
Flanking Region

scholarly journals Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Liu ◽  
Yi Lu ◽  
Wenan Huang ◽  
Zhibo He
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Small Cell ◽  
Expression Level ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Normal Tissues ◽  
Apoptosis Protein

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.

Structure and expression of the human L-myc gene reveal a complex pattern of alternative mRNA processing

1988 ◽  
Vol 8 (1) ◽  
pp. 186-195
Author(s):  
F Kaye ◽  
J Battey ◽  
M Nau ◽  
B Brooks ◽  
E Seifter ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Lung Cancer ◽  
Cancer Cell Lines ◽  
Small Cell ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Myc Gene

We analyzed in detail the structure of the L-myc gene isolated from human placental DNA and characterized its expression in several small-cell lung cancer cell lines. The gene is composed of three exons and two introns spanning 6.6 kilobases in human DNA. Several distinct mRNA species are produced in all small-cell lung cancer cell lines that express L-myc. These transcripts are generated from a single gene by alternative splicing of introns 1 and 2 and by use of alternative polyadenylation signals. In some mRNAs there is a long open reading frame with a predicted translated protein of 364 residues. Amino acid sequence comparison with c-myc and N-myc demonstrated multiple discrete regions with extensive homology. In contrast, other mRNA transcripts, generated by alternative processing, could encode a truncated protein with a novel carboxy-terminal end.

Intrachromosomal rearrangements fusing L-myc and rlf in small-cell lung cancer

1991 ◽  
Vol 11 (8) ◽  
pp. 4015-4021
Author(s):  
T P Mäkelä ◽  
J Kere ◽  
R Winqvist ◽  
K Alitalo
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Human Cancer ◽  
Small Cell ◽  
Chromosome 1 ◽  
Small Cell Lung ◽  
Amino Terminal ◽  
Myc Gene ◽  
Intrachromosomal Rearrangements

Chromosomal abnormalities affecting proto-oncogenes are frequently detected in human cancer. Oncogenes of the myc family are activated in several types of tumors as a result of gene amplification or chromosomal translocation. We have recently found the L-myc gene involved in a gene fusion in small-cell lung cancer (SCLC). This results in a chimeric protein with amino-terminal sequences from a novel gene named rif joined to L-myc. Here we present a preliminary structural characterization of the rlf-L-myc fusion gene, which has been found only in cells with an amplified L-myc gene. In addition, we have used somatic cell hybrids to assign the normal rlf locus to the same chromosome (chromosome 1) on which L-myc resides. Finally, we have been able to establish a physical linkage between rif and L-myc with pulsed-field gel electrophoresis. Our results demonstrate that normal rlf and L-myc genes are separated by less than 800 kb of DNA. Thus, the rlf-L-myc gene fusions are due to similar but not identical intrachromosomal rearrangements at 1p32. The presence of independent genetic lesions that cause the formation of identical chimeric rlf-L-myc proteins suggests a role for the fusion protein in the development of these tumors.

O-191 HER1-HER2-HER3 gene amplification and akt activation inpatients with advanced non-small cell lung cancer (NSCLC) treated with gefitinib

Lung Cancer ◽  
2005 ◽  
Vol 49 ◽  
pp. S63-S64
Author(s):  
F. Cappuzzo ◽  
M. Varella-Garcia ◽  
L. Toschi ◽  
I. Domenichini ◽  
G. Ceresoli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Gene Amplification ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Akt Activation

scholarly journals Overexpressed C14orf166 associates with disease progression and poor prognosis in non-small-cell lung cancer

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Yan-Wu Zhou ◽  
Rong Li ◽  
Chao-Jun Duan ◽  
Yang Gao ◽  
Yuan-Da Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Small Cell ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Expression Levels ◽  
Normal Tissues

Chromosome 14 ORF 166 (C14orf166), a protein involved in the regulation of RNA transcription and translation, has been reported to possess the potency to promote tumorigenesis; however, the role of C14orf166 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of the present study was to assess C14orf166 expression and its clinical significance in NSCLC. Immunohistochemical staining, quantitative real-time PCR (qRT-PCR), and Western blotting were used to detect the C14orf166 protein and mRNA expression levels in NSCLC tissues compared with adjacent normal tissues, as well as in NSCLC cells lines compared with normal human bronchial epithelial cells (HBE). Then, the correlations between the C14orf166 expression levels and the clinicopathological features of NSCLC were analyzed. Additionally, the Cox proportional hazard model was used to evaluate the prognostic significance of C14orf166. We found that C14orf166 expression increased in carcinoma tissues compared with their adjacent normal tissues at the protein (P<0.001) and mRNA levels (P<0.001). High expression of C14orf166 was significantly associated with the T stage (P=0.006), lymph node metastasis (P=0.001), advanced TNM stage (P<0.001), and chemotherapy (P<0.001). Moreover, according to the survival analysis, patients with overexpressed C14orf166 were inclined to experience a shorter overall survival and disease-free survival time (P<0.001). Multivariate COX analysis implied that C14orf166 was an independent prognostic biomarker. Taken together, our findings indicate that the overexpression of C14orf166 may contribute to the disease progression of NSCLC, represent a novel prognostic predictor and help high-risk patients make better decisions for subsequent therapy.

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