Ch5.4

Question 1

1. Q: What discovery linked growth factor receptors to oncoproteins in 1984?

Answer 1

A: The EGF receptor sequence was found to be related to the oncoprotein encoded by the erbB oncogene.

Question 2

2. Q: What virus originally contained the erbB oncogene?

Answer 2

A: The avian erythroblastosis virus (AEV).

Question 2

3. Q: What type of cancer does avian erythroblastosis virus (AEV) induce?

Answer 2

A: Erythroleukemia, a leukemia of red blood cell precursors.

Question 3

4. Q: What important biological areas were united by the discovery of the EGF receptor’s similarity to erbB?

Answer 3

A: Cell biology related to growth factor sensing and retroviral oncoproteins.

Question 4

5. Q: How is the ErbB oncoprotein different from the EGF receptor?

Answer 4

A: The ErbB oncoprotein lacks the N-terminal ectodomain of the EGF receptor.

Question 5

6. Q: What is the consequence of the ErbB oncoprotein lacking the N-terminal ectodomain?

Answer 5

A: It cannot bind EGF but still stimulates cell proliferation.

Question 6

7. Q: How does the truncated EGF receptor function in the absence of EGF?

Answer 6

A: It sends growth-stimulating signals into the cell constitutively.

Question 7

8. Q: In which human cancers were truncated EGF receptors first discovered?

Answer 7

A: In glioblastomas and various other human tumors.

Question 8

9. Q: What type of receptor is associated with poor prognosis in breast cancer?

Answer 8

A: Truncated versions of ErbB2, also known as HER2 or Neu.

Question 9

10. Q: What can mutations in growth factor receptor genes cause?

Answer 9

A: Ligand-independent receptor firing.

Question 10

11. Q: What domains of receptors can mutations affect to cause ligand-independent firing?

Answer 10

A: The transmembrane, ectodomain, and cytoplasmic domains.

Question 11

12. Q: How do growth factors typically activate receptors?

Answer 11

A: By triggering receptor dimerization.

Question 12

13. Q: How does the discovery of ErbB explain cancer cells’ reduced dependence on growth factors?

Answer 12

A: The ErbB oncoprotein sends continuous growth-stimulating signals, mimicking the effect of EGF.

Question 13

14. Q: How do normal cells differ from cancer cells in their need for growth factors?

Answer 13

A: Normal cells require growth factors in culture, while cancer cells often do not.

Question 14

15. Q: What similarity exists between the signals from the ErbB oncoprotein and the EGF receptor?

Answer 14

A: Both release growth-stimulating signals.

Question 15

16. Q: What is unique about the signal sent by the ErbB oncoprotein compared to the EGF receptor?

Answer 15

A: The ErbB oncoprotein sends continuous, unrelenting signals without EGF.

Question 16

17. Q: How are truncated versions of the EGF receptor involved in cancer?

Answer 16

A: They are found in several human tumor types, including glioblastomas and lung cancers.

Question 17

18. Q: What causes the absence of exons 2 through 7 in EGF-R mRNA in some tumors?

Answer 17

A: Deletion of corresponding DNA sequences in the gene for the EGF receptor.

Question 18

19. Q: What is the relationship between EGF receptor overexpression and cancer?

Answer 18

A: Overexpressed or structurally altered EGF receptors are often found in tumors.

Question 19

20. Q: What role do growth factor receptors play in human tumors?

Answer 19

A: They are often overexpressed or structurally altered, contributing to cancer development.

Question 20

21. Q: How does receptor dimerization influence cell signaling?

Answer 20

A: It activates growth factor receptors, leading to signal transduction.

Question 21

22. Q: What kind of growth-stimulating signals do truncated receptors emit?

Answer 21

A: Ligand-independent, constitutive signals.

Question 21

23. Q: How does the deletion of the ectodomain affect EGF receptor function?

Answer 21

A: It allows the receptor to send signals without binding EGF.

Question 22

24. Q: What is the significance of mutations in the transmembrane domain of receptors?

Answer 22

A: They can trigger ligand-independent receptor activation.

Question 23

25. Q: What is the role of the ectodomain in normal EGF receptor function?

Answer 23

A: It recognizes and binds EGF to initiate signaling.

Question 24

26. Q: What happens to cancer cells when they receive constant growth-stimulating signals?

Answer 24

A: They grow and proliferate uncontrollably.

Question 25

27. Q: Why is the discovery of the ErbB–EGF-R connection important for cancer biology?

Answer 25

A: It explains the reduced need for growth factors in cancer cells.

Question 26

28. Q: What does the ErbB oncoprotein mimic in cancer cells?

Answer 26

A: The presence of EGF in the cell’s surroundings.

Question 27

29. Q: What is the functional consequence of receptor mutations in cancer?

Answer 27

A: They may lead to constant growth signal transmission, even without growth factors.

Question 28

30. Q: How are growth factor receptors in tumors structurally altered?

Answer 28

A: They may have mutations or deletions, leading to constitutive activation.

Question 29

31. Q: In which cancer is the EGF receptor most commonly altered?

Answer 29

Glioblastoma

Question 30

32. Q: What feature of HER2/ErbB2 makes it a marker for poor prognosis in breast cancer?

Answer 30

A: Its overexpression or structural alteration.

Question 31

33. Q: What kind of cancer is associated with the avian erythroblastosis virus (AEV)?

Answer 31

Erythroleukemia

Question 32

34. Q: How do alterations in the cytoplasmic domain affect growth factor receptors?

Answer 32

A: They can lead to unregulated signaling.

Question 33

35. Q: How are ligand-independent growth factor receptors typically activated?

Answer 33

A: Through mutations that cause receptor dimerization or structural changes.

Question 34

36. Q: What effect does the continuous signal from the ErbB oncoprotein have on cancer cells?

Answer 34

A: It promotes constant cell growth and proliferation.

Question 35

37. Q: What are some common structural alterations seen in growth factor receptors in cancer?

Answer 35

A: Deletions, mutations in the ectodomain or transmembrane domain, and overexpression.

Question 36

38. Q: How does the loss of ectodomain sequences impact cancer cells?

Answer 36

A: It enables receptors to send signals without external growth factors.

Question 37

39. Q: Why do some cancer cells grow without growth factors?

Answer 37

A: They possess constitutively active, mutated receptors like ErbB.

Question 38

40. Q: What role do truncated EGF receptors play in cancer progression?

Answer 38

A: They allow cancer cells to proliferate without the need for external growth factors like EGF.