
This section deals with current cancer research being conducted at Lawrence Berkeley National Laboratory. It is based on actual interviews with LBNL scientists, and it is somewhat more technical that the rest of the presentation.
Dr. Barcellos-Hoff's research involves examining the way radiation changes the environment in which the cells live. The epithelial cells that she is examining are the ones associated with the mammary glands (breasts). She is examining how healthy tissue cells respond to radiation, and what triggers the repair of these cells when damaged. By studying how the cells respond, she hopes to develop a strategy that might reduce some of the negative side effects that occur during radiation therapy for cancer.
Whenever the body is exposed to ionized radiation, it stimulates a change in the cell's gene expression - that is, what proteins the cell makes. One of the negative results of this change is the development of radiogenic fibrosis , a hardening of the affected tissue that is common following radiation therapy.
The ultimate goal of the research is to identify the events that lead to fibrosis and hopefully block these events. One of the events that has been identified is that ionizing radiation activates an over-production of transforming growth factor-beta (TGFb), a molecule known for its role in producing scar tissue. One aspect of the research involves testing whether TGFb blockers would block fibrosis and therefore reduce the negative side effects of radiation therapy.
One area of Dr. Yaswen's research involves examining the cellular model of an epithelial cell in order to look for substances that are present in normal epithelial cells, but are not present in tumor cells. For example, the lab has isolated a calcium-binding protein which is present only in normal tissue. Dr. Yaswen is trying to find out what are some of the proteins normally found in epithelial cells and whether these proteins sometimes block or interfere with the development of a tumor.
The more opportunities cells have to divide, the greater the probability that some type of cell alteration or DNA damage will induce the onset of cancer. When cells are multiplying rapidly in your body, the natural repair system does not always have a chance to work properly. Dr. Yaswen is trying to find a way to repair the cancer cells' ability to control their own cell division.
Dr. Yaswen's work also could possibly lead to the discovery of genetic markers that may serve to warn of the early onset of cancer.
All cells in the body undergo a process called senescence, which is the natural process of aging and then dying off. There is now increasing evidence that senescent cells accumulate during aging, where they may contribute to the dysfunction of some tissues. In addition, cells can acquire mutations that allow them to "break away" from the control mechanisms of senescence. Such cells are said to be "immortal". This breaking away phenomenon is very common in cancer cells, and immortal cells can lead to metastasis, which is the spreading of the cancer to other parts of the body. By taking a closer look at the senescence of a normal cell, Dr. Campisi hopes to gain a better understanding about the relationship between aging and cancer.
Dr. Campisi's lab also is working closely with Dr. Mina Bissell's lab. They are examining the epithelial cells found in the breast. Through this collaboration, both scientists are hoping to gain a better understanding of how growth and differentiation are regulated in the epithelial cells. There is some evidence suggesting that genes similar to those that control muscle differentiation also may regulate mammary epithelial cells. Since muscle cells undergo a form of differentiation that prevents them from becoming cancer cells, Bissell and Campisi and their colleagues hope to uncover ways to control the growth of breast cancer cells.
By examining over one hundred tumors that are at a similar developmental stage and performing CGH on these tumors, scientists at the lab are trying to find the common region on a chromosome where oncogenes or tumor suppressor genes are most likely to be gained or lost. The portion of the genome that the lab currently is examining lies on Chromosome 20. Metastasis (spreading of the cancer to other parts of the body) is often a fatal occurrence during cancer treatment. By examining other tumors that have metastasized and then completing another CGH, scientists are able to see new regions in the genome where oncogenes or tumor suppressor genes have appeared. By gaining a better understanding of how cancerous genes spread genetically, scientists are hoping to determine the factors that promote the growth and progression of a cancerous cell.
Another tool that is an integral part of Dr. Collins research is fluorescence in situ hybridization (FISH). Using this probe, scientists are able to further isolate the cancer-inducing region of the chromosome. The fluorescent signals that are emitted help to precisely map the possible oncogenes. Eventually, one can determine the exact locations of the oncogenes on the chromosomes. By localizing these genes, scientists are hoping to further the development of molecular therapies. The utilization of these probes may prove to very important for the future treatment of cancer.
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