Homework - Mock Summer Internship Research Problem
In your cell biology course, you learned about the RTK/Ras/MAPK signaling pathway, and
coincidentally, you landed a prized summer internship at Genentech. The lab where you will
work is targeting a cancer driven by a mutation that makes Ras constitutively active. Cancer
cells with this mutation continuously divide out of control. The lab hopes to create a drug that
inhibits the RTK/Ras/MAPK signaling pathway to block the cancer cell proliferation, preventing
uncontrolled cell proliferation. If the Ras signaling activity is blocked, then the cancer cells
cannot grown on soft agar (see Fig 1 below).
Modified from (a) Alida et al 1992 Nature 357: 602; and (b) Serrano et al.1996. 85: 27.
A potential drug that inhibits Ras was identified. So far, the Genentech lab has shown that the
inhibitor blocks the growth factor response in cells (see Fig 2 above). The first two bars of the
histogram shows the effect of growth factor on MAP kinase cascade (final enzyme is ERK
kinase) in non-cancer cells . The last two bars of the histogram shows the effect Ras inhibitor
on cells treated the same as in the first two histogram bars.
Write a proposal (2 page limit) for your summer research internship. Include the following:
1- Give an interpretation of the experiment shown in Fig 2.
2- You are given 2 inhibitors, one that inhibits tyrosine kinase and one that inhibits MAP
kinase. Describe the expected outcome for these 2 inhibitors on cells expressing the
oncogenic, overactive Ras in the cell proliferation assay.