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Molecular evidence for the lack of epidermal growth factor receptor gene expression in small cell lung carcinoma
Abstract:
It has been shown that none of the small cell lung carcinoma (SCLC) cell lines possess epidermal growth factor (EGF) binding activity on their surface. We have examined several SCLC cell lines for the possibility that they may have EGF receptors but that the receptors are masked by an EGF-like protein factor(s), which may be produced by an autocrine mechanism. No evidence, however, was found for the production of such factors. We then used an EGF receptor complementary DNA to determine the state of the EGF receptor gene by Southern blot analysis. The receptor gene appears to be present in these cells in an intact, unrearranged form. These cells, however, were found to lack detectable levels of EGF receptor mRNA, suggesting a possible reason for the absence of EGF receptors on the cell surface. Furthermore, karyotype analysis revealed that SCLC cell lines Lu134 and H69 contained a morphologically normal chromosome 7, which carries the EGF receptor gene. Also, these SCLC cells contained the apparently normal chromosome 3 and exhibited the presence of c-raf-1 gene in an unrearranged form. Thus, the previously noted partial deletion of chromosome 3 is not necessarily common to the SCLC cells. Instead, the lack of EGF receptor is frequently found in SCLC cell lines and is distinct from the other types of lung cancer. We postulate that SCLC cells have some active regulatory mechanism which prevents the expression of EGF receptor gene.
Insights
Small cell lung carcinoma (SCLC) cell lines lack epidermal growth factor (EGF) receptors. This absence is due to a lack of EGF receptor mRNA, not gene alteration, suggesting a regulatory mechanism prevents gene expression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Small cell lung carcinoma (SCLC) cell lines typically do not exhibit epidermal growth factor (EGF) binding activity.
- Previous hypotheses suggested masked EGF receptors due to autocrine EGF-like factors, but this was not supported by evidence.
Purpose of the Study:
- To investigate the underlying reasons for the absence of EGF receptors on SCLC cell surfaces.
- To determine if the EGF receptor gene is present and intact in SCLC cells.
- To explore potential regulatory mechanisms affecting EGF receptor expression in SCLC.
Main Methods:
- Southern blot analysis using EGF receptor complementary DNA to assess the EGF receptor gene.
- Analysis of EGF receptor mRNA levels.
- Karyotype analysis of chromosomes, including those carrying the EGF receptor gene (chromosome 7) and c-raf-1 gene (chromosome 3).
Main Results:
- The EGF receptor gene is present in an intact, unrearranged form in SCLC cell lines.
- Detectable levels of EGF receptor mRNA are absent in these cells.
- Normal chromosome 7 (carrying the EGF receptor gene) and chromosome 3 were observed in analyzed SCLC cell lines, and the c-raf-1 gene was unrearranged.
Conclusions:
- The absence of EGF receptors on SCLC cell surfaces is primarily due to a lack of detectable EGF receptor mRNA, not gene mutations or rearrangements.
- This molecular characteristic distinguishes SCLC from other lung cancer types.
- A regulatory mechanism likely prevents the expression of the EGF receptor gene in SCLC cells.