Question

5. Ninety percent of cancer deaths are caused by metastatic rather than primary tumors. Define metastasis. Explain the rationale for the following new cancer treatments: (a) batimastat, an inhibitor of matrix metalloproteases and of the plasminogen activator receptor, (b) antibodies that block the function of integrins, integral membrane proteins that mediate attachment of cells to the basement membrane and extracellular matrices of various tissues.

8. Distinguish between proto-oncogenes and tumor-suppressor genes. To become cancer-promoting, do proto-oncogenes and tumor-suppressor genes undergo gain-of-function or loss-of-function mutations? Classify the following genes as proto-oncogenes or tumor-suppressor genes: p53, ras, BCL-2, JUN, MDM2, and p16.

15. Pancreatic cancers often possess loss-of-function mutations in the gene that encodes the Smad4 protein. How does this mutation promote the loss of growth inhibition and highly metastatic phenotype seen in pancreatic tumors?

Answer 1

Metastis is the direct extension and penetration by cancer cells into neighboring tissues or distant tissues. Some cancer cells known as circulating tumor cells acquire the ability to penetrate the walls of lymphatic or blood vessels, after which they are able to circulate through the bloodstream to other sites and tissues in the body.

Cancer cells stimulates the growth of new blood vessels to ensure the supply of oxygen and nutrients. Matrix metallo proteases are important regulators of angiogenesis (new blood vessels sprouting) and its production increased by cancer cells. Batimastat inhibits this enzyme and inhibits angiogenesis as a result nutritional sources of cancer cells arrested.

The integrin family of cell adhesion receptors regulates progression and metastasis of solid tumors. Integrins directly bind components of the extracellular matrix (ECM) and provide the traction necessary for cell motility and invasion. ECM remodelling is also controlled by integrins, which regulate the localization and activity of proteases. In addition to their well-established role in migration and invasion, integrins can regulate proliferation. So Monoclonal antibodies that inhibits integrin receptors can suppress cancer spread.

A proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. It under goes gain of function mutations. A tumor suppressor gene, or anti-oncogene, is a gene that regulates a cell during cell division and replication. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function; in combination with other genetic mutations this could allow the cell to grow abnormally.

P53 - tumor suppressing gene

Bcl2 gene family contains both proto oncogenes and tumor suppressing gene

Ras- proto oncogene

Jun- proto oncogene

MDM2- proto oncogene

P16 - tumor suppressing gene