Biomedical Engineering Reference
In-Depth Information
younger age, decrease cancer risk. These factors influence either the number or
activation of breast stem cells. Several drugs able to decrease cancer risk and/or
cancer reoccurrence have been developed. These include agents reducing the
production of estrogen or blocking its action on cells. Similarly the removal of
the ovaries reduces cancer risk in those with an extensive family history of
breast and ovarian cancer (Kauff et al., 2002). Mutations in the BRCA1 and
BRCA2 genes dramatically increase the risk of breast cancer. However, unlike
many other tumor suppressor genes, BRCA1 or BRCA2 mutations are not
commonly found in sporadic breast tumors. The BRCA1 and BRCA2 proteins
play a role in the DNA repair process. These mutations can be thought of as
increasing the probability of genetic events associated with tumor progression.
Since these genes are not in the main pathway leading to the breast cancer, they
are not frequently mutated in sporadic tumors, but do increase an individual's
risk of disease, when mutated.
In tissues such as the colon or skin, undergoing a constant level of renewal of
the cells, the stem cells are dividing at a slow but constant rate. In the absence of
disruption of these tissues, the risk of cancer is low. However, activation of stem
cells in renewal tissues can occur by inflammation or by tissue damage caused by
radiation, mutagens, and irritants (Rakoff-Nahoum, 2006; Trosko, 2005; Trosko
and Tai, 2006). Chronic tissue damage would cause an increased rate of division
of the renewal tissue stem cells and increase the available number of target cells
for transformation. Colon cancer provides one of the best examples of the
influence of inflammation on cancer. Inflammatory diseases such as Crohn
disease and inflammatory bowel disease result in dramatically increased risk for
colon cancer (Eaden, 2004). Patients with mutations in the APC gene have
familial adenomatous polyposis coli (FAP) syndrome and suffer from large
numbers of colon polyps (Groden et al., 1991 Nishisho et al., 1991). Polyps are
pre-malignant lesions and FAP subjects have an elevated risk for colon cancer
(Gardner, 1962). Individuals withFAP, as well as the mice withmutations inApc,
have an increased cellular proliferation compartment in the colon (Deschner and
Lipkin, 1975; Moser et al., 1992; Su et al., 1992). The effect of APCmutations has
been proposed to be to increase the proliferation of colonic stem cells (Knudson,
1993). Consistent with this model, the APC gene ismutated in the vast majority of
sporadic colon tumors (Kinzler and Vogelstein, 1996). Additional downstream
events in colon cancer are very well characterized and include mutations in P53,
RAS, and other genes (Kinzler and Vogelstein, 1996).
12 SP Cells in Tumors and Cell Lines
Once it was recognized that stem cells were predominantly found in the Side
Population (SP) fraction, it became possible to sort and purify stem cells from
virtually any population of cells or tissues. SP cells were identified in 15 of 23
neuroblastoma samples and in neuroblastoma, breast cancer, lung cancer, and
