Question

Questions 1. Consider the Kaplan-Meier plot below and answer the following questions. This plot is measuring the proportion of patients who did not die of breast cancer relative to total levels of cyclin E, years after diagnosis. Total 17 pts Note: It is important that you pay attention to the highlighted words (bold, underlined). If you don't understand what Explain or Molecular or mean, please come see me a. Explain the Kaplan-Meier plot, relating cyclin E levels to cancer progression and to the Note the words Progression and Clinical. 6 pts Provide at least two molecular explanations for why the levels of cyclin E may be higher in the breast epithelial cells. Hint: Think about the normal pattern of cyclin E expression and how this pattern could be altered. 6 pts c. Discuss the direct molecular consequences of increased cyclin E levels to cell cycle progression. That is, saying increased proliferation is not enough. 5 pts stage III disease low total cyclin E levels 0.8 0.6 0.4 high total cyclin E levels 0.2 8 10 years after diagnosis

Answer 1

1.

a) The Kaplan-Meier plot shows the relation between breast cancer progression and the level of cyclin E in the breast epithelial cells, with that of survival. From the plot, it can be seen that the levels of cyclin E are inversely proportional to the survival of breast cancer patients. The plot shows that patients with low levels of cyclin E show higher chances of survival and vice versa. Furthermore as the years of diagnosis progresses, the level of cyclin E increases and the chances of survival decrease.

b) The levels of cyclin E are high in breast epithelial cells in the case of breast cancer because -

• Cyclin E is a cyclin dependent kinase which is important for the initiation of DNA duplication in the cell cycle. In cancer cells, DNA duplication is very high and this is possible only if cyclin E levels are high. Hence, cyclin E over expression might be one reason for its high levels in cancer cells.
• Cyclin E isoforms are comparatively small and have a low molecular weight. These isoforms can bind with CDK2 easily as they are resistant to CKIs. The size of cyclin E isoforms can hence accelerate cell cycle progression.

c) The role of cyclin E is to bind to Cdk2 of the G₁ phase, which is essential for the transition from G₁ to S phase of the cell cycle. This initiates DNA duplication. So, a high level of cyclin E will accerate this process, leading to a very high number of duplicated DNA and multiple cell cycles. All of this leads to proliferation of cancer cells.