This web page was created as an assignment for an undergraduate course at Davidson College.
Curing Cancer: The Breast Cancer Gene?
Structure Of The Brct Repeat Region From The Breast Cancer Associated Protein, Brca1. From the Protein Database.
What is breast cancer?
In breast cancer, malignant cells invade the breast tissue area. One in nine women will develop breast cancer in her lifetime and over 160,000 new cases are diagnosed each year. Hereditary breast cancer accounts for 5% - 10% of all breast cancer cases (Oncolink, 2002). Many studies within the past 10 years have sought to identify causes of hereditary breast cancer, and the research has yielded many susceptibility genes. The two most common genes are BRCA1 and BRCA2, dubbed as the "breast cancer genes."
BRCA1
The BRCA1 gene is located on chromosome 17. To see the DNA coding sequence of this gene, click here. It encodes a 220-kD phosphoprotein normally located in the nucleus, suggesting that it plays a role in transcriptional regulation (Chen et al., 1995).
There are numerous allelic variations in this gene and its protein product also seems to interact with a number of other proteins. For a recent article concerning BRCA1 and the role it plays in regulating and/or affecting other genes, go to Medwire. The actual journal article abstract may be found in Pubmed. These researchers used DNA microarray analysis to identify targets of the BRCA1 protein. It is a functional analysis of the BRCA1 gene.
BRCA2
The BRCA2 gene is located on chromosome 13 and encodes over 3000 amino acids. It appears that BRCA2 plays an important role in male breast cancer that BRCA1 may not play. Many researchers have suggested that BRCA2 encodes a tumor repressor working through DNA repair mechanisms. See OMIM.
BRCA2 is located at locus 13q12. Click on the ideogram to see what genes are around BRCA2.
Mutations in these two genes seem to play important roles in breast cancer, but how do they interact? What do they do? What sorts of mutations cause breast cancer? There are a number of different questions and there are pages upon pages of research being done to answer these questions quickly because breast cancer is such a serious disease. What this webpage hopes to discuss is the difference between what researchers really report in scientific journals and how the media portrays these reports in the "popular press." I only analyze two articles: one from Science magazine and another from MSNBC.com, but this provides a good example of the difference between such reports.
Scientific vs. Sensational
Now, my grandmother always told me to believe nothing of what I hear and only half of what I see. I can’t say that I still hold to that axiom, but I do know that the media does indeed tend to ignore key facts when reporting the “news” and sometimes they stretch the facts they tell in order to make the story more sensational. One such example of these popular press stories is the “gene for ______” story. Pick a human trait or characteristic and fill in the blank. With so much new technology, genes are popping up everywhere for everything from dyslexia to a predisposition to gaining weight.
We hear or read these stories and the press uses words like “the cure” or “genetic screening.” Does finding the gene for a disease necessarily mean that doctors and researchers have developed a way to help those who have that disease? Not necessarily, but the news reporter might allude to such a treatment and our minds automatically think that maybe in the near future an answer is imminent. What we as the general public do not see is the science behind the report, the data supporting the claim, and the researchers admitting that this may only be the first of many steps toward finding a cure.
The September 26, 1994, Time article, “Cornering a Killer,” tells the story of identifying the location of the BRCA1 gene, a gene supposedly responsible for a hereditary form of breast cancer. Investigators had been unable to locate the exact location of BRCA1 on human chromosome 17 until the time of this article. Within the first paragraph, the author discusses the search for the location of the gene and reports that even Science magazine made “the unusual concession” of releasing the articles describing the finding three weeks prior to their publication. In 1994 this was considered a huge breakthrough, as Dr. Funmi Olopade states in the article, “Finally we are beginning to crack open the mystery” (Nash, 1994).
Eight years later, investigators are still trying to “crack open the mystery.” An MSNBC.com article from June 13, 2002, reports that researchers who were looking into the genetic causes of Fanconi anemia (a disease that causes bone marrow failure in children) found that six genes linked to the Fanconi pathway were also linked to the BRCA1 and BRCA2 genes. Because BRCA1 and BRCA2 mutations only account for about 10% of cases of breast cancer, there are obviously other causes. The research team at Harvard University that stumbled on these six new genes believes that they may be related to causes of breast cancer that cannot be blamed on BRCA1/BRCA2 mutations (Howlett, 2002).
The article at MSNBC.com mentions the Science article that officially reports these findings. Researchers had cloned six Fanconi anemia (FA) genes that interact in a common pathway, but were previously unable to identify two other genes corresponding to FA-B and FA-D1. They report previous evidence linking the two breast cancer susceptibility genes to the FA genes and then discuss their investigation into the relationship between these two gene types. The investigators first sequenced the BRCA1 and BRCA2 genes in cells from FA-B and FA-D1 patients and found no BRCA1 mutations. However, biallelic mutations were detected in BRCA2. Two significant mutations cause frameshifts, resulting in truncated BRCA2 proteins.
They next examined BRCA2 protein expression in the FA-B and FA-D1 phenotypes and found that expression levels corresponded with what they knew from the DNA sequences. And finally, the researchers transfected cells containing the biallelic BRCA2 mutations with cDNA that encoded the full-length wild-type BRCA2 protein. Correctly transfected cells expressed full-length BRCA2. These cells also exhibited a correction of their mytomycin C sensitivity. Originally, these cells were hypersensitive to mytomycin C, a characteristic of Fanconi anemia. However, they became resistant to mytomycin C when the full-length wild-type BRCA2 protein was being expressed. This, along with all the other results mentioned in the paper, confirm for the researchers that BRCA2 is an FA gene.
Both reports discuss that researchers found a gene related to both Fanconi anemia and to breast cancer. However, while the “popular press” article claims that that gene, the BRCA2 gene, is directly linked to six other genes in the FA pathway (and now possibly a breast cancer pathway), the Science article makes no such claim, but only alludes to a common pathway. “These similarities suggest that BRCA2 and other FA proteins cooperate in a common DNA damage response pathway, the FA/BRCA pathway” (Howlett, 2002). Furthermore, this article discusses a “model” for the genes’ associations with one another, but does not present any evidence. The MSNBC.com article claims in its title “Six more genes tied to breast cancer.”
Giant leaps are made from one article to the next. The last sentence in the scientific article says, “The precise molecular function(s) of BRCA1 and BRCA2 in this [FA] pathway remain to be elucidated” (Howlett, 2002). Without this information, how can “new drugs” be found, as the popular press suggests? With these new discoveries, the team supposedly reports that they hope new drugs can be discovered to delay or treat cancer and Fanconi anemia. However, without the exact knowledge of what these genes do and how they indeed interact in the same pathway, it will be difficult for pharmaceutical companies to develop drugs or therapies centered around them. This is the first approach to identifying the genes in the pathway, but the next step involves examining the genes from a functional standpoint and determining their exact roles. Supposedly the genes interact to form an enzyme that helps repair damaged DNA, but even the MSNBC.com article only mentions this once and the Science article only suggests that.
The main difference then between the articles in the sensationalism. The popular press article stresses “therapies” and “drug treatment,” while the Science article alludes to none of that. People want to hear about drugs and cures, not about a common genetic pathway. The popular press then prints what more people will read. However, on a personal note (not to mention a genomics side), these articles are important because of their nature concerning many genes that work together and that not just “one gene” is the cause of breast cancer (or in this case, of Fanconi anemia). Any genes in the pathway can be mutated, developing a faulty protein that goes on to affect any other genes or proteins it interacts with. “The importance of this finding is that it connects two previously different bodies of work on DNA repair” (Witt and Ashworth, 2002). Hopefully this in itself will aid in this research’s progress.
References
Fox, Maggie. 2002. "Six More Genes Tied to Breast Cancer." http://www.MSNBC.com. Accessed 10 September 2002.
Howlett, N.G., et al. 2002. "Biallelic Inactivation of BRCA2 in Fanconi Anemia." Science. 297:606-609.
Nash, J.M. 1994. "Cornering a Killer." Time Magazine. 26 September 1994.
Witt, E. and A. Ashworth. 2002 "D-Day for BRCA2." Science. 297:534
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