Chapter 34 Study Guide

What is the difference between a benign tumor and a malignant tumor?

-benign tumor: abnormal cells remain at the original site; do not cause serious problems and can be removed by surgery -malignant tumor: includes cells who spread to new tissues & impair the functions of one or more organs; aka transformed cells

What is a protooncogene and what does it encode?

-normal versions of cellular genes -code for proteins that stimulate normal cell growth and division

How does the chemotherapeutic agent Taxol inhibit tumor growth?

-prevents microtubule depolymerization, freezing mitotic spindle-this stops cells from proceeding past metaphase & leads to their destruction

Transformation is the conversion of a normal cell to a tumor cell. A. What does the process of transformation involve?

-the development of a malignant tumor involves a gradual accumulation of mutations that convert proto-oncogenes to oncogenes & knock out tumor-suppressor genes-a ras oncogene and a mutated p53 tumor-suppressor gene are often involved-about a half dozen DNA changes must occur for a cell to become fully cancerous-these changes usually include the appearance of at lease 1 active oncogene + the mutation/loss of several tumor-suppressor genes

Patients undergoing chemotherapy are subject to infection, lose much of their hair, and suffer from extreme nausea. Why?

-the side effects of chemotherapy are due to the effects of the drugs on normal cells for example:-nausea results from effects on intestinal cells-hair loss from effects on hair follicle cells-susceptibility to infection from effects on immune system cells

How does the tissue shown in lecture 34, slide 5 demonstrate the central dogma of cancer?

-there is a loss of normal gene expression profile --> mass of tissue (retinoblastoma) that does not carry out normal function

What is the usual fate of transformed cells?

-transformed cells often have altered proteins on their surface-thus, the body's immune system recognizes the cell as "non-self" & destroys it (apoptosis)

How does the treatment of a benign tumor differ from the therapy used against metastatic tumors?

A tumor that appears to be localized may be treated with high-energy radiation, which damages DNA in cancer cells much more than DNA in normal cells, apparently because the majority of cancer cells have lost the ability to repair such damage. To treat known or suspected metastatic tumors, chemotherapy is used, in which drugs that are toxic to actively dividing cells are administered through the circulatory system.

How would mutation of a tumor suppressor gene lead to cancer?

Any mutation that decreases the normal activity of a tumor-suppressor protein may contribute to the onset of cancer, in effect stimulating growth through the absence of suppression.

What is a tumor suppressor gene?

In addition to genes whose products normally promote cell division, cells contain genes whose normal products inhibit cell division. Such genes are called tumor-suppressor genes since the proteins they encode help prevent uncontrolled cell growth. Tumor suppressors are factors that inhibit the cell cycle, cell motility, and angiogenesis.

How is a proto-oncogene converted to an oncogene?

In general, an oncogene arises from a genetic change that leads to an increase either in the amount of the proto-oncogene's protein product or in the intrinsic activity of each protein molecule. The genetic changes that convert proto-oncogenes to oncogenes fall into four main categories: epigenetic changes, translocations, gene amplification, and point mutations. Examples of proto-oncogenes that become oncogenes when mutated are: Ras G-protein and tyrosine kinase receptors, Epidermal growth factor receptor (EGF-R), human epidermal growth factor receptor 2 (HER2)

Would a Ras mutation be autosomal dominant or recessive?

Mutant tumor-suppressor alleles are usually recessive & most oncogenes behave as dominant alleles

What is the effect on the cell when the Ras protein is mutated?

Normally, such a pathway will not operate unless triggered by the appropriate growth factor. But certain mutations in the ras gene can lead to production of a hyper- active Ras protein that triggers the kinase cascade even in the absence of growth factor, resulting in increased cell division

The p21 protein is a tumor suppressor that halts the cell cycle in order to allow for DNA repair. Would mutation of p21 be autosomal dominant or recessive?

Recessive

) Oncoproteins and mutated tumor suppressors interfere with cell-cycle-stimulating pathways or cell-cycle-inhibiting pathways, respectively. A. What is the normal function of the Ras protein?

The Ras protein, encoded by the ras gene (named for rat sarcoma, a connective tissue cancer), is a G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases.

What is the central dogma of cancer?

The loss of normal structure leads to the loss of normal function and uncontrolled cellular proliferation.

Describe why the function of p53 makes this protein the "guardian of the genome".

The p53 gene has been called the "guardian angel of the genome." Once the p53 protein is activated—say, by the ATM protein, a protein kinase, after DNA damage—p53 activates several other genes, such as p21. The p21 protein halts the cell cycle by binding to cyclin-dependent kinases, allowing time for the cell to repair the DNA. Researchers recently showed that p53 also activates expression of a group of miRNAs that inhibit the cell cycle. The p53 protein can also turn on genes directly involved in DNA repair. If DNA damage is irreparable, p53 activates "suicide" genes, whose protein products bring about programmed cell death (apoptosis; see Figure 11.20). Thus, p53 acts in several ways to prevent a cell from passing on mutations due to DNA damage.

What is the effect on the cell when p53 is mutated?

The p53 gene, named for the apparent molecular weight of its protein product, is a tumor-suppressor gene. The protein it encodes is a specific transcription factor that promotes the synthesis of cell cycle-inhibiting proteins. That is why a mutation that knocks out the p53 gene or in a gene required to activate the p53 protein (for example, a gene called ATM) can lead to excessive cell growth and cancer.

List the various functions of tumor suppressor proteins.

The protein products of tumor-suppressor genes have various functions. Some repair damaged DNA, which prevents the cell from accumulating cancer-causing mutations. Other tumor-suppressor proteins control adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial in normal tissues and is often absent in cancers. Still other tumor-suppressor proteins are components of cell-signaling pathways that inhibit the cell cycle.

List five characteristics of a malignant cancer cell.

These cells may have unusual numbers of chromosomes, though whether this is a cause or an effect of tumor-related changes is an ongoing debate. Their metabolism may be altered, and they may cease to function in any constructive way. Abnormal changes on the cell surface cause cancer cells to lose attachments to neighboring cells and the extracellular matrix, allowing them to spread into nearby tissues. Cancer cells may also secrete signaling molecules that cause blood vessels to grow toward the tumor. A few tumor cells may separate from the original tumor, enter blood vessels and lymph vessels, and travel to other parts of the body.

What is angiogenesis?

growth of new blood vessels

What is metastasis?

spread of cancer cells to locations distant from their original site