BURCH- APRIL 20, 2013 THE BIOLOGY OF CANCER Short Answer : Please be concise with your answers and as specific as possible. 1. Genes involved in cell cycle activity/survival are mutated to contribute...

The Biology of Cancer
1. Genes involved in cell cycle activity/survival are mutated to contribute to the
development of cancer. Name the two categories of genes related to cell division that are
mutated and how mutations affect their function and lead to cancer.
There could be observed several such genes that are responsible for regulation of cell-
cycle, but because of mutation, might lead towards development of cancer. The rationale behind
such correlation between cell-cycle regulatory genes and their susceptibility of being cancerous
is their close relationship with cellular machinery controlling the proliferation of cell.
There are chiefly two groups of such genes known as; oncogenes and tumor suppressor genes.
Oncogenes may be defined as; mutated versions of genes that take part in stimulation of
cell proliferation. When mutation activates these genes then the protein encoded by them are
modified in such way that their transformation activity is enhanced. This can be understood via
taking the example of RAS oncogenes that encode for proteins exhibiting guanosine-nucleotide-
binding activity and intrinsic guanosine triphosphatase activity. It has been examined by
researchers that mutation in the 12, 13, or 61 codon of RAS genes results into such protein that
could remain active in a continuous manner, and might transduce the signals through connecting
the tyrosine kinases to downstream serine and threonine kinases. Such persistent signals may
stimulate uninterrupted growth of a cell (Chamberlain et al., 1975).
On the other hand, Tumor suppressor genes usually inhibit the cellular growth, assist in
DNA repairing, and govern apoptosis (also known as; PCD (Programmed Cell Death)). So; as a
consequence of improper functioning/inactivation of tumor suppressor genes, their growth-
inhibitory ability might fail, and cells can grow in an uncontrollable manner due to which, cancer
can occur. For example, due to aberration of TP53 gene apoptosis can get affected in an adverse
mode since; it requires the participation of p53 protein which is encoded by TP53 gene. Such
failure of apoptosis results into persistent growth and division of cells with damaged DNA that
can ultimately lead towards development of cancer (Coleman et al., 1975).
2. How can active transport activity by cells contribute to cancer?
Active transportation activity of cell is essential for transfer of diverse vital molecules,
but can also be linked with cancer in a frequent manner for instance, prostate cancer is
considered as; the leading cause of death in males. Out of several factors which might contribute
in development of prostate cancer deficiency of Zinc is also a key reason. In fact, prostatic
glandular epithelium is able to accumulate high levels of Zn because of ZIP1 that can be
regarded as; an important Zn uptake transporter, but might be identified in a down-regulated
form in the cancerous cells. Because of such reduced activity of Zn transporter, the level of Zn
may also get reduced inside the malignant cell (Engzell et al., 1971).
Further, activity of ZIP2 and ZIP3 could also become less in malignant cell than normal
one due to which, the Zn accumulation ability of cell might be declined in a significant manner.
Such diminished active transport as well as storage activity of cell can ultimately result into
manifestation of cancerous cells as; Zn can exhibit tumor suppressor and DNA repairing
activities. Another contribution of active transport activity of cell in development of cancer
might be identified in the case of ABC transporters which may pump...