Cancer Biology Health Article

Definition

Cancer is the second leading cause of death in the United States, with one out of every three Americans falling victim to it at some point in their lives. It is a disease of unregulated cell growth. The knowledge gained in cancer biology over the past 20 years has allowed for the discovery of new, highly targeted drugs to treat cancer.

Causes of cancer

The molecular cause of cancer involves mutations in the nuclear DNA (the genetic material in cells) that can be caused by chemicals, viruses, radiation or spontaneous mutations. Although much importance has been put on chemicals and environmental pollutants as carcinogens (agents that cause cancer), it actually turns out that the predominant factors in determining cancer are associated with lifestyle. For instance, cigarette smoking accounts for 30% of cancers in males. Dietary factors are associated with another 35% of all human cancers. It is estimated that with dietary improvements there could be a 50% reduction in colon and rectal cancers, a 25% reduction in breast cancer and 15% reductions each in prostate, endometrial and gallbladder cancers. Other cancers that might be decreased by dietary improvements include cancer of the stomach, esophagus, pancreas, ovaries, liver, lung and urinary bladder. This adds up to 9% reduction in overall deaths. It is estimated that if Americans doubled their intake of fruits and vegetables and fiber and decreased their fat intake by 25%, significant advances could be made. Obesity also puts an individual at an increased risk of death for uterus, gallbladder, kidney, stomach, colon, and breast cancers. Obese women have a 55% greater risk of mortality from cancer than women of normal weight, while men are at a 33% greater risk of mortality. Alcohol and lack of exercise are also associated with increased risk for cancer.

Cell growth

Normal growth of cells is a highly regulated cellular function. The stimulus to begin cell division comes from growth factors that react with growth factor receptors on the surface of the cell. After the binding of growth factor to a growth factor receptor, the growth message is carried from the surface of the cell to the nucleus through a cascade of biochemical reactions referred to as signal transduction. Once the signal reaches the nucleus, transcription factors bind to the DNA, which turns on the production of proteins involved in growth and division of the cells.

DNA contains genetic information that encodes proteins involved in all aspects of cell metabolism. If a gene is damaged or mutated, the protein it encodes will be affected. DNA mutations can result in an altered expression of protein; either too much or too little, or in altered forms of a protein that either do not perform their function or perform it differently. Damage to genes that encode for proteins regulating cell growth such as oncogenes, tumor suppressor genes and DNA repair genes can result in alterations in cell growth and thus cancer.

Oncogenes

Oncogenes are altered forms of normal genes called proto-oncogenes. There have been over 100 oncogenes identified so far. Their primary role in the cell is in regulation of growth. They encode growth factors, growth factor receptors, transcription factors that regulate the manufacturing of new proteins and signal transduction proteins. Signal transduction refers to the process of transmitting a signal from the outside layer of the cell, through the cytoplasm into the nucleus of the cell and begins with a growth factor and receptor interaction. Cancer cells sometimes have altered levels of growth factors or their receptors or factors involved in signal transduction. For example, the K-ras oncogene is an example of a mutated signal transduction protein involved in cancers such as colon and lung cancer, and the HER2/neu oncogene is a mutated receptor associated with breast cancer. Finally, this series of biochemical reactions reaches the nucleus to affect gene transcription, or the reading of genes into RNA and protein. This occurs via transcription factors. Mutations in transcription factors result in abnormal levels of certain proteins that can result in cancer. Myc is an example of a transcription factor mutated in lung cancer.

Tumor suppressor genes

Also called anti-oncogenes, tumor suppressor genes code for proteins that halt cell growth. In the normal cell, when DNA has become damaged, the cell stops growing to devote time to repairing DNA. Factors responsible for allowing this repair to take place are tumor suppressor genes. If tumor suppressor genes malfunction, the cells do not stop dividing when DNA is damaged and the mutation is then carried over to the daughter cells after cell division. This increases the risk of developing cancer. In hereditary cancers it is often a malfunctioning tumor suppressor gene that is inherited. Although there are two copies of each tumor suppressor gene, the second gene can take over the role if it is not mutated. A mutation in the second copy of the gene is required for total loss of tumor suppressor function. There are dozens of tumor suppressor genes identified that are involved in cancer including p53 (identified with many cancers) and APC in colon cancer, and BRCA-1 in breast cancer.

Characteristics of cancer cells

Cancer cells appear differently than normal cells do under the microscope. Their nucleus is much larger than in normal cells, their chromosomes are irregular in distribution and the nucleoli in the nucleus are very prominent. When cancer cells are grown in culture in the lab they also appear different than normal cells. Rather than growing in neat single-layer sheets with one next to the other they grow more haphazardly. They have long processes that extend from the cells, they overlap one another and their shape is more rounded. Normal cells will continue to divide and grow in a culture plate until they touch a neighboring cell where they receive a signal to stop growing. Cancer cells, on the other hand, do not receive this signal and grow on top of each other forming piles of growing cells that resemble a tumor.

Normal cells require growth factors added to their growth medium to enable them to grow in culture. Cancer cells do not require the same amount of growth factors, possibly because they are able make their own growth factors. Normal human cells will grow for a short amount of time in culture and then die, while cancer cells tend to keep on growing. The term given for this ability is immortalization. Cancer cells in culture are immortalized or have unlimited growth potential.

Cancer cells also have a more immature appearance compared to normal cells. This is referred to as dedifferentiation, or they lack differentiation. As an embryo matures and develops, its cells differentiate. This means they take on more specific roles that are reflected in their appearance—kidney cells begin to look different than skin cells or breast cells. Cancer cells look less and less like the tissue they are part of and more like embryonic cells. They also produce embryonic proteins that are used as tumor markers such as carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP).