History of Research
DCC's biological role in cancer has had a long, controversial history. Although DCC has been studied for many years, a significant amount of the data collected is contradictory and much of the focus has been on getting clear picture of the basics.
When the genetic abnormalities that occur in advanced colorectal cancer were first identified, one of the most frequent events was found to be loss of heterozygosity (LOH) of region 18q21. One of the first genes sequenced in this region was DCC, and it was subsequently analyzed for tumour suppressor activity. However, the lack of somatic DCC mutations made it seem likely that the nearby SMAD2 and SMAD4 genes were the reason for 18q21 LOH. The fact that DCC heterozygotes had no increased rates of cancer, even when crossed with mice carrying Apc mutations, solidified this viewpoint. The finding that DCC was a receptor for netrin-1 involved in axon guidance initially moved research away from DCC in cancer. It was later realized that DCC may be involved in directing cell motility, which has direct implications for metastatic cancer.
The first direct evidence for DCC as a tumour suppressor gene was published in 1995. Researchers found that addition of DCC to an immortalized cell line suppressed tumorigenicity rather definitively. However no mechanism for this suppression was obvious, and it took several years to propose one.
Nearly ten years after DCC was discovered, studies were published that showed that DCC was involved in apoptosis. Instead of studying loss of DCC as was commonly done, the authors looked at human embryonic kidney cells transfected with DCC. They found an increase in apoptosis that corresponded to DCC expression, which was completely eliminated when netrin-1 was co-transfected or simply added to the media.
When it was understood that DCC apoptosis may also be overcome by netrin-1 overexpression, colorectal cancers were assessed for netrin-1 overexpression, and a small but significant percent of these cancers were found to vastly overexpress the molecule.
Read more about this topic: Deleted In Colorectal Cancer
Famous quotes containing the words history of, history and/or research:
“... that there is no other way,
That the history of creation proceeds according to
Stringent laws, and that things
Do get done in this way, but never the things
We set out to accomplish and wanted so desperately
To see come into being.”
—John Ashbery (b. 1927)
“Considered in its entirety, psychoanalysis won’t do. It’s an end product, moreover, like a dinosaur or a zeppelin; no better theory can ever be erected on its ruins, which will remain for ever one of the saddest and strangest of all landmarks in the history of twentieth-century thought.”
—Peter B. Medawar (1915–1987)
“The research on gender and morality shows that women and men looked at the world through very different moral frameworks. Men tend to think in terms of “justice” or absolute “right and wrong,” while women define morality through the filter of how relationships will be affected. Given these basic differences, why would men and women suddenly agree about disciplining children?”
—Ron Taffel (20th century)