Expression of c-myc in Progenitor Cells of the Bronchopulmonary Epithelium and in a Large Number of Non-Small Cell Lung Cancers

Abstract

We performed in situ hybridization for c-myc, N-myc, and L-myc mRNA expression using 35S-labeled cRNA probes on frozen sections of 19 pairs of non-small cell lung cancers (NSCLC) and the surrounding non-neoplastic lung tissue. In non-neoplastic lung, c-myc expression was strongest in bronchial epithelium basal cells and hyperplastic alveolar type II pneumocytes, which are potential progenitor cells for bronchopulmonary epithelium and their tumors. In contrast, N-myc and L-myc mRNAs were not detected in non-neoplastic lung. In studies of freshly resected primary tumors, expression of c-myc was detected in 11 of 19 NSCLC (with the highest levels in squamous cell carcinomas), two of which also expressed L-myc, while N-myc expression was never detected. Levels of c-myc expression in tumors were significantly higher than in non-neoplastic lung samples. We conclude that: (1) c-myc expression in non-neoplastic lung tissues is highest in bronchial basal cells and hyperplastic type II cells, and (2) in NSCLC, overexpression of the myc-proto-oncogene is common.

Development of pulmonary bronchiolo-alveolar adenocarcinomas in transgenic mice overexpressing murine c- myc and epidermal growth factor in alveolar type II pneumocytes

“…The role of c-myc overexpression as a first step in the process of tumour formation was further confirmed by the gene dosage effect observed in homozygous transgenics, which showed accelerated tumour development in the lung. These findings support the hypothesis that this gene is causally involved in the development of human alveolar lung bronchiolo-alveolar adenocarcinomas, where overexpression of c-myc is frequently observed (Broers et al, 1993;Lorenz et al, 1994). Overexpression of IgEGF under the control of the SP-C promoter led to the formation of hyperplasias of the alveolar epithelium in the lung of transgenic mice, whereas overexpression of TGFα in the lung of transgenic mice has been shown to induce enlarged parenchymal airspace and pulmonary fibrosis (Hardie et al, 1997).…”

“…Several proto-oncogenes, including c-myc and the transforming growth factor α (TGFα) as well as its homologue, epidermal growth factor (EGF), are frequently found to be overexpressed in human pulmonary carcinoids and adenocarcinomas (Battista et al, 1993;Broers et al, 1993;Lorenz et al, 1994;Moody, 1996), suggesting that they may be directly involved in lung carcinoma formation. c-myc is a member of a group of regulatory proteins which are involved in controlling cell cycle entry, progression and differentiation (reviewed in Facchini and Penn, 1998).…”

Stage-specific embryonic antigen-4is expressed in basaloid lung cancer and associated with poor prognosis

“…c-myc represents one of the factors that is crucially involved in the early steps of somatic cell reprogramming and is the centre of a regulatory network that induces an embryonic gene expression profile, albeit with no pluripotency in cancer cells [38,39]. Depending on the method, 5.6-80% of all NSCLCs show an amplification of this gene and 48-58% an overexpression [40][41][42]. Remarkably, in normal tracheobronchial epithelium, the highest expression values were reported for basal cells, and tumours arising from these natural progenitor cells might per se display ESC features [42].…”

CITED2 functions as a molecular switch of cytokine-induced proliferation and quiescence

“…[10][11][12][13][14] MYC, a potent oncogene, is highly expressed in bronchial epithelium basal cells and hyperplastic alveolar type II pneumocytes. 15 Through the regulation of E2F transcription factor expression, MYC has a critical role in cell cycle control. 16,17 Among the E2Fs, E2F3 is overexpressed in most lung cancers 18 and is induced by EGFR to transactivate genes involved in the G1/S transition.…”