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Negative Selection and Chromosome Instability Induced by Mad2 Overexpression Delay Breast Cancer but Facilitate Oncogene-Independent Outgrowth
Summary
This article discusses the effects of Mad2 overexpression on chromosome instability and breast cancer. The authors demonstrate that overexpression of Mad2 with Kras(G12D) or Her2 in mammary glands of adult mice results in mitotic checkpoint overactivation, mitotic arrest, and cell death. Despite this, Mad2 expression persists and increases karyotype complexity in Kras tumors, resulting in a higher frequency of developing persistent subclones that avoid remission and continue to grow.
Q&As
What impact does Mad2 overexpression have on breast cancer?
Mad2 overexpression delays breast cancer tumor onset and leads to mitotic arrest and cell death.
How does Mad2 overexpression affect chromosome instability?
Mad2 overexpression leads to mitotic checkpoint overactivation and increases karyotype complexity.
How does Mad2 overexpression interact with oncogene withdrawal?
Mad2 overexpression creates a selective pressure of oncogene withdrawal.
Does Mad2 overexpression lead to a higher frequency of persistent subclones after oncogene withdrawal?
Yes, Mad2-positive tumors have a higher frequency of developing persistent subclones that avoid remission and continue to grow.
What evidence shows that Mad2 overexpression delays Her2-driven breast tumorigenesis?
Time-lapse imaging of organotypic cultures and pathologic analysis prior to tumor establishment shows that Mad2 overexpression delays Her2-driven breast tumorigenesis without affecting aneuploidy.
AI Comments
👍 This article provides an in-depth analysis of the role of Mad2 overexpression in delaying breast cancer and facilitating oncogene-independent outgrowth.
👎 This article fails to provide sufficient evidence to support its conclusions regarding the effect of Mad2 overexpression on breast cancer.
AI Discussion
Me: It's about how overexpression of the mitotic checkpoint protein Mad2 can delay breast cancer but can also facilitate oncogene-independent outgrowth.
Friend: That's really interesting. What are the implications of this?
Me: Well, it implies that the overexpression of Mad2 can be beneficial in delaying the onset of cancer, but it can also lead to increased chromosome instability which could lead to the growth of persistent subclones that don't respond to oncogene withdrawal. This could make it more difficult to treat and could lead to relapse.
Action items
- Research the effects of Mad2 overexpression on other types of cancer.
- Investigate the potential of Mad2 overexpression as a therapeutic strategy for breast cancer.
- Analyze the impact of chromosomal instability on the development and progression of breast cancer.
Technical terms
- Negative Selection
- A process in which cells with certain characteristics are eliminated from a population.
- Chromosome Instability
- A condition in which chromosomes are abnormally arranged or have extra or missing pieces.
- Mad2 Overexpression
- The increased expression of the mitotic checkpoint protein Mad2.
- Oncogene
- A gene that has the potential to cause cancer.
- SCNA
- Single-nucleotide polymorphism-based copy number analysis.
- Aneuploidy
- A condition in which a cell has an abnormal number of chromosomes.
- Mitotic Checkpoint
- A mechanism that monitors the accuracy of chromosome segregation during cell division.