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bcl-2 expression is reciprocal to p53 and c-myc expression in metastatic human colorectal cancer
R A Popescu1, A Lohri, E de Kant
1Division of Oncology, Kantonsspital Basle, Switzerland.
Abstract:
Apoptosis (programmed cell death) inhibition may be an important mechanism by which gastrointestinal mucosal cells containing damaged DNA evade normal clearance mechanisms and grow to become invasive tumours. Since bcl-2 is an apoptosis inhibitor, bcl-2 mRNA expression was measured in 21 metastases of colorectal cancer using reverse transcription-polymerase chain reaction analysis. The mean bcl-2 mRNA expression (0.45 U, P < 0.0001) was lower than that of normal mucosal controls (= 1 U). p53 expression was inversely correlated with bcl-2 expression (P = 0.021) in 19 evaluable samples, and in tumours where p53 expression was over twice that of normal colonic mucosal values, bcl-2 mRNA was significantly decreased (mean 0.30, P = 0.0052). c-myc was also inversely correlated with bcl-2 expression (P = 0.025). Decreased bcl-2 expression in metastatic colorectal cancer may be partly due to allelic loss, given the proximity of bcl-2 to the frequently deleted DCC gene on chromosome 18q. However, the inverse correlation to p53/c-myc suggests an active downregulation of bcl-2, possibly following delegation of its apoptosis inhibiting role to other genes.
Insights
Inhibition of apoptosis by bcl-2 may promote colorectal cancer. This study found lower bcl-2 mRNA in metastatic colorectal cancer, inversely correlated with p53 and c-myc expression.
Area of Science:
- Molecular Biology
- Oncology
- Gastroenterology
Background:
- Apoptosis (programmed cell death) inhibition is implicated in cancer development.
- The bcl-2 gene is a key inhibitor of apoptosis.
- Gastrointestinal mucosal cells with DNA damage may evade clearance, leading to tumors.
Purpose of the Study:
- To investigate bcl-2 mRNA expression in colorectal cancer metastases.
- To explore the relationship between bcl-2, p53, and c-myc expression in these tumors.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify bcl-2 mRNA.
- bcl-2 mRNA expression was compared between 21 colorectal cancer metastases and normal mucosal controls.
- Correlations between bcl-2, p53, and c-myc expression were analyzed.
Main Results:
- Mean bcl-2 mRNA expression was significantly lower in colorectal cancer metastases (0.45 U) compared to normal controls (1 U).
- p53 expression was inversely correlated with bcl-2 expression (P = 0.021).
- Tumors with elevated p53 showed significantly decreased bcl-2 mRNA (mean 0.30, P = 0.0052).
- c-myc expression was also inversely correlated with bcl-2 expression (P = 0.025).
Conclusions:
- Decreased bcl-2 expression is a feature of metastatic colorectal cancer.
- The inverse correlation with p53 and c-myc suggests active downregulation of bcl-2.
- Allelic loss on chromosome 18q may contribute to reduced bcl-2, but active regulation is also indicated.