Columnar epithelial cells from the colonic mucosa are studied to identify abnormalities in cell signaling pathways. Abnormal epithelial cells from colonic adenocarcinoma are shown to have a mutation that blocks hydrolysis of GTP-bound active RAS. Normal columnar cells have active RAS protein that undergoes hydrolysis to the inactive GDP-bound form. Which of the following signaling pathways is most likely abnormally stimulated in the carcinoma cells?

a. Jak-Stat Pathway
b. MAP kinase pathway
c. p53
d. Both a & b

I think its MAP kinase pathway because RAS is part of MAP kinase pathway that ultimately leads to transcription and expression of genes but if GTP is not hydrolyzed then RAS will be constantly activated leading to continued gene expression that may lead to cancer but I am not completely sure about it because p53 is also a tumor suppressor gene.

  • $\begingroup$ Is this a homework/test question? It looks a lot like one. $\endgroup$ – Resonating Jul 10 '14 at 18:42
  • $\begingroup$ Homework questions are off-topic unless you show some effort of solving them yourself. What are your thoughts about it? $\endgroup$ – Chris Jul 10 '14 at 18:44
  • $\begingroup$ Hi, this very much sounds like a homework question! It will be great if you show some evidence of what you think the likely answer is and why so that any input would be constructive! $\endgroup$ – Behzad Rowshanravan Jul 10 '14 at 18:46
  • $\begingroup$ I think it is MAP kinase pathway because if GTP is not hydrolyzed then it will lead to constant activation of RAS as RAS is in MAP kinase pathway..so what is your opinion..? $\endgroup$ – emi Jul 10 '14 at 19:15
  • $\begingroup$ Perhaps also take a look at Jak-stat and see what pathways influences it! and as correctly mentioned p53 is an inhibitor so it can't be the right answer! $\endgroup$ – Behzad Rowshanravan Jul 11 '14 at 15:12

The answer is b, as the mutation constantly activates the RAS protein. RAS is part of the MAP-Kinase pathway, constant signaling of it permanently activates this pathway and leads to changes in gene expression. See the image below:

enter image description here

If you are interested in more details, have a look at these papers:

  • $\begingroup$ Whoever downvoted my answer, what is your problem with it? I can (and will) improve it, when you can tell what you think is wrong with it. $\endgroup$ – Chris Jul 21 '14 at 10:05
  • $\begingroup$ yeah you are right that both are involved in cancer but in question a specific condition is mentioned that is "mutation in RAS" and it is constantly activated that leads to cancer so its only MAP kinase pathway...as no RAS in JAK-STAT pathway..by the way I didn't downvote your answer.. $\endgroup$ – emi Aug 13 '14 at 12:09
  • $\begingroup$ @emi Yes, you are right. I missed that point somehow. Adapted the answer. $\endgroup$ – Chris Aug 13 '14 at 14:13

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