Transformation is the genetic alteration of a cell resulting from the uptake of external genetic material. Transformed cells exhibit characteristics like genetic instability, immortalization, abnormal growth control, and tumorigenicity. Transformation can occur spontaneously, through viral infection, or exposure to carcinogens or radiation. Transformed cells are studied to understand cancer properties by culturing cells from tumors or transforming normal cells using viruses or chemicals.
3. INTRODUCTION
In molecular biology, transformation is
the genetic alteration of a cell resulting from
the direct uptake and incorporation
of exogenous genetic material from its
surroundings through the cell membrane.
“Transformation” has a special meaning in
relation to animal cells, indicating
progression to a cancerous state, the process
is usually called “transfection”.
4. Sometimes eukaryotic cells exhibit unusual
and alternative growth characteristics both in
culture and in vivo. Such cells are usually
referred to as transformed or neoplastic cells
.The transformation of some cells may be
induced using viruses.
5.
6. HISTORY
Transformation in bacteria was first demonstrated in 1928 by the British
bacteriologist Frederick Griffith.
Griffith was interested in determining whether injections of heat-killed
bacteria could be used to vaccinate mice against pneumonia. However,
he discovered that a non-virulent strain of Streptococcus
pneumoniae could be made viulent after being exposed to heat-killed
virulent strains.
Griffith hypothesized that some "transforming principle" from the heat-
killed strain was responsible for making the harmless strain virulent.
In 1944 this "transforming principle" was identified as being genetic
by Oswald Avery, Colin MacLeod, and Maclyn McCarty.
They isolated DNA from a virulent strain of S. pneumonia and using just
this DNA were able to make a harmless strain virulent.They called this
uptake and incorporation of DNA by bacteria "transformation".
7. CAUSESOFTRANSFORMATION
Transformation of cells may occur due to any
one of the following causes that ultimately
result in a changed genetic material:
Spontaneous.
Infection with transforming virus.
From gene transfection.
Exposure to chemical carcinogens.
Exposure to ionizing radiations.
10. Genetic Instability:
In general, the cell lines in culture are prone
to genetic instability. A majority of normal
finite cell lines are usually genetically stable
while cell lines from other species (e.g.
mouse) are genetically unstable, and can get
easily transformed.The continuous cell lines
derived from tumors of all species are
unstable.
11. Immortalization:
The acquisition of an infinite life span by a cell
is referred to as immortalization. Most of the
normal cells (from different species) have a
finite life span of 20-100 generations. But
some cells from mouse, most of the tumor
cells have infinite life span, as they go on
producing continuous cell lines.
12. Immortalization can be done by-
Controlling the finite life span of cells.
By viral genes.
By human fibroblast.
By telomerase induction.
13. Aberrant Growth Control:
The transformed cells and the cells from tumors,
grown in culture show many aberrations with
respect to growth and its control.
Anchorage independence:
There occur several changes on the cell surfaces
of transformed cells.These include alterations in
the cell surface glycoproteins and integrin’s, and
loss of fibronectin. Some of the transformed cells
may totally lack cell adhesion molecules (CAMs).
14. Contact inhibition:
The transformed cells are characterized by
loss of contact inhibition.This can be
observed by the morphological changes in
the disoriented and disorganized monolayer
cells.This results in a reduced density
limitation of growth, consequently leading to
higher saturation density compared to
normal cells.
15. Low serum requirement:
In general, transformed cells or tumor cells
have lower serum dependence than the
normal cells.This is mostly due to the
secretion of autocrine growth factors by the
transformed cells.
16. Some of the growth factors produced by tumor cells are
given:
Colony stimulating factor (CSF).
Transforming growth factor (TGFa).
Interleukins 1, 2 and 3.
Vasoactive intestinal peptide (VIP).
Gastrin releasing peptide.
It may be noted that many normal cells (fibroblasts,
endothelial cells) also produce autocrine factors during
active stage of cell proliferating. Hence, these factors will
not be of much use to serve as markers of cell
transformation.
17. Tumorigenicity:
Cell transformation is a complex process that
often results in the formation of neoplastic
cells.The cell lines obtained from malignant
tumors are already transformed.
18. CHALLENGES
Such cells may undergo further
transformation in the in vitro culture due
to:
Increased growth rate.
Immortalization.
Reduced anchorage dependence.
For the malignant transformation of cells,
several steps may be required.
19. Two approaches to understand malignant-
associated properties of cultured cells:
The cells can be cultured from malignant
tumors and characterized.
Viral genes or chemical carcinogens can be
used to transform the untransformed cells.
20. CONCLUSION
Transformed cells are changed from normal cells to
cells with many of the properties of cancerous cells.
Some of these cell lines have actually been derived
from tumors or are transformed spontaneously in
culture by mutations.
Chemical or gamma ray treated cells can become
infinite with loss of growth factors.
Viral infection with SV40T antigen can insert
oncogenes and lead to gene alterations.
No matter how transformation occurs the result is a
cell with altered functional morphological and
growth characterstics.