Question

Choose three genes associated with your chosen cancer below. Answer the following questions for each gene.

Ovarian Cancer genes:

• AKT1 • CDH1 • PTEN • TP53 • RAD50 • RB1

What is the function of the gene?

• Is this a tumor suppressor or proto-oncogene? Why?

• Which hallmarks are associated with the gene? If there are no hallmarks explain how the gene relates to cancer.

• Find a molecular diagram related to the role of this gene in cancer. Create a linear molecular diagram of the illustrated pathway.

You may use your text book or find an image on the web.

• Where would you intervene for a targeted therapeutic approach?

– Would you activate or inhibit this target?

Answer 1

The tumor cells differ from their normal counterparts in many respects: growth control, morphology, cell-to-cell interactions, membrane properties, cytoskeletal structure, protein secretion, and gene expression. We also saw that two broad classes of genes — proto-oncogenes (e.g., ras) and tumor-suppressor genes (e.g., APC) — play a key role in cancer induction. These genes encode many kinds of proteins that help control cell growth and proliferation; mutations in these genes can contribute to the development of cancer.

Most cancers have inactivating mutations in one or more proteins that normally function to restrict progression through the G₁ stage of the cell cycle (e.g., Rb and p16), although colon carcinomas usually do not. Virtually all human tumors have inactivating mutations in proteins such as p53 that normally function at crucial cell-cycle checkpoints, stopping the cycle if a previous step has occurred incorrectly or if DNA has been damaged. Likewise, a constitutively active Ras is found in several human tumors of different origin. Thus normal growth control and malignancy are two faces of the same coin.

An oncogene formed by the first mechanism encodes an oncoprotein that differs slightly from the normal protein encoded by the corresponding proto-oncogene. In contrast, the latter two mechanisms generate oncogenes whose protein products are identical with the normal proteins; their oncogenic effect is due to their being expressed at higher-than-normal levels or in cells where they normally are not expressed. However they arise, the gain-of-function mutations that convert proto-oncogenes to oncogenes act dominantly; that is, mutation in only one of the two alleles is sufficient for induction of cancer.

Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration.