P53 the gene that decoded the

cancer
Cancer is a beast because it seems
unstoppable.
Down to their innate molecular core, cancer
cells are hyperactive, survival-endowed,
scrappy, fecund, inventive copies of
ourselves.
Siddhartha Mukherjee, The Emperor of All
Maladies: A Biography of Cancer

Cancer's life is a recapitulation of the body's

life, its existence a pathological mirror of our
own.
Siddhartha Mukherjee, The Emperor of All
Maladies: A Biography of Cancer
All cancers are alike but they are alike in a
unique way.
Siddhartha Mukherjee, The Emperor of All
Maladies: A Biography of Cancer
5 likes

Cancer destroy man in a unique and

appalling way, as flesh of his own flesh
which has somehow been rendered
proliferative, rampant, predatory and
ungovernable.(Peyton Rous)
The emperor of all maladies is undoubtedly
the cancer.
Most of the cancer till now have no
treatment practically when they are
diagnosed and all most all of them are
deadly.But the most horrifying part of the
cancer is that it takes a decent time to kill a
patient and when a patient is diagnosed
with cancer he has almost nothing to do but
just wait and count his or her days.This
disease is equally disaster for the patients
family not only due to heavy economical
burden but also for heavy mental stress.Its
not easy to assure your dearest when both
of you know that you cant do anything or to
see your dearest dying everyday slowly.
But still the one question that obsessed me
that why cancer is so rare?I know it will
startle you as all of we read in our pathology

books cancer is second leading cause of

death in United states and one in three of us
will be diagnosed with cancer at some point
in our lives and one in four of us will die of
the disease.But looking at cancer from the
viewpoint of the cells, It is just one rogue
cell which has lost its normal regulatory
machine and trigger cancer, where billions
and billions of cells in our bodies that are
growing and replicating all the time without
producing a tumour.
Now a days we live with mutagens and
carcinogens.They are everywhere in our
food,beverages,air,water. Even with few
rupees we can buy one of most potent
carcinogen from a cigarette stall. Our gene
is bombered by this deadliest substance
each and everyday but still chance of arising
cancer from those billions cells in our body
is almost zero.
A measure of just how resistant our cells are
to corruption is the fact that a goodly chunk
of our DNA natures instruction manual for
building our bodies can be traced
back to the original single-celled organism
known as the last universal common

ancestor of all life on earth (often referred

to by the acronym LUCA), whose existence
was first
proposed by Charles Darwin in his book On
the Origin of Species, published in 1859. In
other words, some of our genes are more
than 3.5 million years old and have been
passed down
faithfully from one generation to the next
over unimaginable eons of time.----Gerard
Evan
Cancer do arise but clearly we have some
magnificent mechanisms to restrict the
spontaneous evolution of cancer cells in our
body
Today there are almost 200 types of cancer
and most of them have very distinctive
characteristics feature but all cancers are
alike they are alike in a unique way.
All cancer share a common core ,there is
some genetic alteration or in a better way
there is mutation in p53 gene. There are
several ways by which a cell become
cancerous see najeeb

Cancer was not disorganized chromosomal

chaos. It was organized chromosomal
chaos
I know what you are thinking what this p53
gene does but the better question is what it
doesn't . In a single word p53 gene is the
guardian of our genome. It is like a
policeman. Whenever there is any lethal
injury it halts our cell cycle and cells cannot
divide. So no chance of devoloping cancer.
But it is not as simple as I describe here . It
is equivalent or much more harder than
rocket science and I am not going to discuss
all these molecular mumbo jumbos in
here(as I know very little of it) which you
can find any standard textbook rather I am
interested to tell some of it history which is
not found in textbook
In the 1970s, cancer researchers made
substantial efforts to study how tumor
viruses transform normal cells into cancer
cells to gain knowledge about how
malignant tumors form. It was clear that
some RNA tumor viruses package mutated
copies ( oncogenes) of certain host genes,
which enable the viruses to induce abnormal

proliferations in host cells. The mechanism

through which DNA tumor viruses cause
cancer, however, was still an enigma, since
unlike RNA tumor viruses, DNA tumor
viruses encode their own genes that are not
homologous to mammalian genes. The
proteins expressed from the DNA tumor viral
genome in the inoculated host animals are
called tumor antigens, because they are
recognized as foreign by the immune
system, resulting in antiserum production.
Exploring how DNA tumor virus induces
cancer, researchers concentrated on a small
DNA tumor virus, Simian Virus 40 (SV40),
that codes for two tumor antigens, small t
antigen and large T antigen. Pinpointing
interactions between tumor antigens,
cellular proteins, and antisera, several
studies converged to demonstrate the
existence of p53 protein in a variety of
cancer cells. - See more at:
https://embryo.asu.edu/pages/discoveryp53-protein#.dpuf
Discovery of p53
In 1979 six groups of investigators
independently reported the discovery of a
~53 kDa protein that was present in human
and mouse cells. Five of these studies

showed that this protein bound to the large

T-antigen of SV40 in cells infected with this
virus, and the sixth found it expressed in
several types of mouse tumour cells. Various
investigations carried out on this protein
(p53), and later on the gene (TP53),
suggested that it was an oncogene. This
interpretation, which reflected the research
climate of that time, was based on
apparently compelling experimental
evidence: the p53 protein was bound to the
major oncogenic protein of SV40, which
strongly suggested that it was a
downstream effector of the large T-antigen
pathway; high levels of p53 expression were
found in many cancers; and the
overexpression of an apparently wild-type
TP53 gene transformed a normal cell into a
cancer cell. Although there were a few
experimental observations that did not fit
with the idea that TP53 was an oncogene,
the existence of tumour suppressor genes
was hypothetical in the mid-1980s and so
there was little reason to think otherwise.

In 1979 six groups of investigators

independently reported the discovery of a
~53 kDa protein that was present in human
and mouse cells. Five of these studies
showed that this protein bound to the large
T-antigen of SV40 in cells infected with this
virus, and the sixth found it expressed in
several types of mouse tumour cells. Various
investigations carried out on this protein
(p53), and later on the gene (TP53),
suggested that it was an oncogene. Though
the two men most widely credited with
finding the super-gene are David Lane and
Arnie Levine, who published their research
in the most prestigious journals, Nature and
Cell respectively.
In the 1970s, can-cer researchers mainly
focused on cancer-causing viruses. In
particular, it became evident that such
viruses carried oncogenes. But how did
these viral oncogenes transform cells and
produce tumours in animals? It was
proposed that the DNA tumour virus oncogenes encode viral proteins that indirectly
lead to the excessive induction of cellular

oncoproteins which leads to excessive cell

proliferation.
SV40, which stands for simian vacuolating
virus 40 ( It was named for the effect it
produced on infected green monkey cells
which developed an unusual number of
vacuoles. )was very popular among
researchers in that time because it provides
a simple model for exploring how the
machinery of cells DNA, genes and
proteins works in complex organisms,
including us. The virus was discovered in
1960 by American microbiologist Maurice
Hilleman. Like other polyomaviruses SV40
has potential to cause tumours. Tumours
that are induced in experimental animals by
small DNA tumour viruses, such as simian
virus 40 (SV40), typically express few viral
proteins. These proteins are recognised by
the immune system of the host, leading to
the production of antibodies against them.
By the mid 1970s, such antibodies started to
gain popularity as tools to identify and
monitor proteins encoded by the viral
genome and expressed in trans-formed
cells. On the basis of their mode of
detection, these proteins were termed viral
tumour antigens. Subsequent genetic

analysis revealed that the genes encoding

these viral tumour antigens were often
those also responsible for the transforming
activity of the virus, namely the viral
oncoprotein. In the case of SV40, the two
viral proteins identified in this manner were
called large and small T-antigen,
respectively. It is important to study these
large and small T antigens proteins to know
how it alter the genetic architecture of host
cell. And that is what David Lane a scottish
immunologist was doing at the Imperial
Cancer Research Fund(ICRF) in London
under the guidance of Lionel Crawford.
Lanes main task was to develop reagents,
or to highlight and extract the large T
antigen protein from infected cells and
separate it from all the other gunge in the
cells.
The process he used to harvest the large T
antigen was called electrophoresis, which
involves passing an electric current through
a gel sandwiched between glass plates to
which the protein
mixture has been added in little wells. The
current causes the protein molecules to
migrate through the gel according to their

size and electrical charge and help to

separate them. The large molecules
dont go far, while the little ones go a long
way. But no matter how hard Lane tried, he
never seemed able to get the large T
antigen pure. There was always this
nagging shadow in the gel. a non-viral
protein with an apparent molecular mass of
around 53 kDa came along for the ride.
Others in Lanes lab told him that his tools
were not as good as he imagined and some
suggested the rogue protein was a
breakdown product of the large T antigen.
But Lane trusted his tools, antibodies
designed to recognise only large T antigen
and no other protein; he had been
extremely careful to avoid contamination of
his experiments. Here Lanes background in
immunology came in useful. He knew if two
proteins were sticking to each other
physically, an antibody that recognised one
would automatically bring down the other. It
strengthened his conviction that the
interaction between the two was central to
the way large T antigen turned the cells
cancerous. He was able to get enough
evidence to support that view and publishd
the findings with Lionel Crawford in nature
on 26th April 1979.