Devita, Hellman, and Rosenberg's Cancer

LWBK1006-01 LWW-Govindan-Review November 24, 2011 11:17

Chapter 1•Molecular Biology of Cancer Part 1 13

can occur. For example, the presence of a normal karyotype is a well-

recognized observation in acute myelogenous leukemia and gives impor-

tant clinical information conferring an intermediate prognosis. The loss

of a single X or Y chromosome is a normal variant commonly observed

in older patients. It carries little clinical significance.

Answer 1.24. The answer is A.

Hayflick and Moorehead documented a landmark finding of cell biol-

ogy when they observed that normal eukaryotic cells would only repli-

cate approximately 50 to 100 times before dying. This limited replicative

capacity of nontransformed cells is called the “Hayflick phenomenon.”

It is now known that the ends of the chromosomes, called “telomeres,”

gradually shorten, losing 25 to 200 base pairs with each round of divi-

sion. After 50 to 100 rounds of division, the telomeres reach a critically

shortened length, triggering cell senescence. Telomeres can be maintained

by the enzymatic activity of telomerase, which function to restore and

maintain telomeres at their full length. Activation of telomerase is a key

mechanism by which some cells, such as cancer cells, evade senescence.

Although gene defects occur spontaneously in cells and will lead to pro-

grammed cell death, this usually occurs in the immediate generation after

the defect is established. Tumor growth does require neovascularization,

but the “Hayflick phenomenon” applies to programmed senescence in

nontransformed cells.

Answer 1.25. The answer is C.

Telomerase is the DNA polymerase that synthesizes the repeating six base

pair motif (TTAGGG) that comprises the ends of all chromosomes. It

is a nucleoprotein with both a protein and RNA component. With cell

division, the telomere ends become progressively shorter until a critical

length is reached and programmed cell death is initiated. Synthesizing and

repairing the ends of the shortening telomeres allows cells to maintain the

integrity of the chromosomal ends and is important for cells that need to

divide without reaching senescence, such as cancer cells. In light of this, it

is not surprising that the majority of cancer cells overexpress telomerase,

but there are cancers that appear to have invoked alternative mechanisms

to repair telomeres. Indeed, telomerase-deficient (deleted) mice can be

induced to develop tumors.

Answer 1.26. The answer is C.

Senescence refers to a state in cultured cells where growth arrest is perma-

nent. Senescence differs from quiescence in that quiescent cells can reen-

ter the cell cycle in response to appropriate mitogenic cues. Quiescence is

generally induced by serum starvation, growth factor deprivation, high-

density growth, and transient DNA damage. Senescence can be induced by

prolonged DNA damage, oxidative stress, telomere shortening, and onco-

gene activation. Additional differences include uninducible c-fos expres-

sion in response to serum stimulation and increased PAI expression in

senescence versus quiescence.