Related Experiment Videos
Microsatellite instability is associated with the loss of apoptosis in ductal breast carcinomas
1Centro de Oncologia Molecular, Institut de Recerca Oncològica, Hospital Duran i Reynals, Ciutat Sanitaria i Universitaria de Bellvitge (CSUB), Barcelona, Spain.
Abstract:
Metastatic progression in ductal breast carcinomas are related to apoptosis in primary tumors. Frameshift mutations in a single-repeat sequence within the coding region (G)8 of the pro-apoptotic Bax gene have been related to microsatellite instability (MSI) and progression of some carcinomas and lymphomas. The aim of this study was to explore whether the extended lifespan of breast cancer cells can also be triggered by Bax mutation in ductal-breast carcinomas, and whether breast cancer cell MSI is related to the loss of apoptosis. For this purpose we studied frameshift mutations of a microsatellite (G)8 in the third exon of the Bax gene in a series of 105 ductal breast carcinomas, at T1 and T2-3 stages, 45 of which had lymph node metastasis. We analyzed MSI in five sequences of DNA isolated from normal and tumor tissue samples taken from 86 patients, and we explored the relationship between MSI and tumor apoptosis status. Bax mutation was not present in ductal breast carcinomas. MSI (two or more markers altered) was detected in 11.6% of tumors. Loss of apoptosis occurred in 80% (8/10) tumors with MSI, versus 17.8% of tumors without MSI (chi2 test, p = 0.0004), independently of Bax protein expression. We conclude that frameshift mutations of a microsatellite (G)8 of the Bax gene are not critical for the loss of apoptosis in breast cancer, and that loss of apoptosis may be a consequence of overexpression of anti-apoptotic protein Bcl-2 or Bcl-xL. Moreover, MSI in breast carcinomas might be the cause of loss of an apoptotic pathway that is not induced by frameshift mutations of a microsatellite (G)8 of the Bax gene.
Insights
Microsatellite instability (MSI) in breast cancer is linked to a loss of apoptosis, but not by Bax gene mutations. This loss of programmed cell death may be due to other factors, impacting cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastatic progression in ductal breast carcinomas is associated with apoptosis in primary tumors.
- Microsatellite instability (MSI) and Bax gene mutations are implicated in the progression of some cancers.
- The pro-apoptotic Bax gene contains a microsatellite repeat prone to frameshift mutations.
Purpose of the Study:
- To investigate if Bax gene mutations contribute to the extended lifespan of breast cancer cells.
- To determine if MSI in breast cancer is associated with a loss of apoptosis.
- To explore the relationship between MSI, Bax mutation, and apoptosis in ductal breast carcinomas.
Main Methods:
- Studied frameshift mutations in the (G)8 microsatellite of the Bax gene in 105 ductal breast carcinomas.
- Analyzed MSI in DNA from normal and tumor tissues of 86 patients.
- Assessed the relationship between MSI and tumor apoptosis status.
Main Results:
- Bax gene mutations were absent in the studied ductal breast carcinomas.
- MSI was detected in 11.6% of tumors.
- Loss of apoptosis was significantly higher in tumors with MSI (80%) compared to those without MSI (17.8%), independent of Bax expression.
Conclusions:
- Frameshift mutations in the Bax gene's (G)8 microsatellite are not a cause of apoptosis loss in breast cancer.
- MSI in breast carcinomas may lead to the loss of apoptotic pathways.
- Overexpression of anti-apoptotic proteins like Bcl-2 or Bcl-xL might contribute to the loss of apoptosis.