Critical Thinking

In phosphorylated ERK1/2 show an increase compared to

 In regards to figure
1, there were higher levels of EGFR detected in TNBC cells in comparison to non
TNBC cell line MCF- 7, thus no express EGFR is shown. With regards to
phosphorylated EGFR there is an increase of level only due to TNBC cell line.
EGFR expression was observed due to the highest and lowest levels in MDA MB 468
and SUM 1315 cell lines. In TNBC cell line a high quantity of phosphorylated
AKT and phosphorylated ERK1/2 show an increase compared to MCF 7 cells.
Distinctively AKT and ERK1/2 expression shows a low TNBC cell line compared to
MCF 7 cells.


Antibodies such as MDA-MB-468 and SUM-1315 cell lines both
inhibited proliferation after 20 to 30 % in comparison to untreated cells, thus
no effect is shown in MDA-MB-231 and HCC-1937 cell lines. An antibody
concentration of 10 ?g/mL is shown to be used to achieve a growth inhibitory as
it stayed stable for higher concentration. The figure shows a mechanism of
resistance to anti-EGFR mAbs as MDA-MB-231 and HCC-1937 cell lines appeared.

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Figure 2 demonstrates a dose independent manner from one EGFR-TKIs
as it inhibited proliferation. Gefitinib and erlotinib was more active on
MDA-MBA-468 as it shows differential effect on figure 2. Furthermore figure 2
shows the IC50 was not achieved as SUM-1315 cells was quite sensitive to




Table 1: shows monoclonal antibodies with combination of anti
EGFR and single agent of erlotinib and gefitinib of its IC50 value 

Table 1 shows the summery of gefitinib and
erlotinib as one agent in amalgamation with centuximab and panitumumab of the
half inhibitory concentration value.  Table
1 also shows MDA-MB-468 cell line of cetuximab ominously increased the effect
of cytotoxicity of gefitinib and erlotinib ranging from concentration of 1 to
20 ?M.
Alternatively the table shows there is an increase of growth inhibitory in all
concentration which is an effect of EGFR-TKIs, thus this was caused due to
SUM-1315 cell line and mAbs extremely increasing the growth inhibitory.
Panitumumab ominously increased the effect of gefitinib (5.9) and erlotinib (1.7)
at all concentrations, thus similar values also shows with cetuximab.

Figure 3: In regards to MDA-MB-468 cells after
cetuximab and panitumumab treatment phosphorylated ERK1/2 was down controlled
by 2.5 fold and 5 fold. According to figure 3,
EGFR-TKI reduced the phosphorylation of ERK1/2 to 10 fold in comparison to
untreated cells. Furthermore the phosphorylation of ERK1/2 is less
effective than erlotinib due to the courses of mAbs and gefitinib blocked it in
SUM-1315 cell line.  Compared to
untreated cells ERK1/2 was decreased by 2 fold and 10 fold by gefitinib and
erlotinib. The ERK1/2 phosphorylation is suppressed due to the combination of
panitumumab or cetuximab.  The activation
status of RAS/MAPK pathway in regards to its effectiveness was associated to
anti-EGFR therapies seen on the cell viability.

Alternatively the results
propose inhibiting EGFR phosphorylation and decreasing ERK1/2 activity respond
to TNBS cell lines to anti EGFR-targeted therapies.


In regards to figure 4 and figure 5 the
cell cycle distribution was not effected by mAbs and neither did it effect HC
1937 cell line and the apoptotic cells in MDA-MB-231. However an
anti-proliferation effect was present as it shown in the result, thus in part, on
induction of cell cycle arrest at G1 phase and apoptosis.


3.0 Discussion

Cetuximab or panitumumab is not linked
with tumour expression of EGFR according to previous studies on mCRC that
showed the likelihood response. (Reference tumors 35–37). The
cell cycle and the apoptotic profile after treatment was consistent due to the
anti EGFR therapies on TNBC cell of growth inhibitory.

Compared to other treatments, gefitinib possessed a
greater inhibitory effect on cell cyle, thus including greater levels of
apoptosis. Alternatively according to the results obtained it suggest that a
combination of gefitinib and anti-EGFR mAbs should be considered a suitable
method for the dual targeting of EGFR in TBC. (Reference)


The level of phosphorylated ERK1/2
was reduced due to most treatments reducing the activity of EGFR in the cell
line. However ERK1/2 inactivation is the main aspect of predicting response to
EGFR inhibitors. (Reference)


The downstream of signaling of
pathways of EGFR was investigated by
Baselga, et al. thus suggested that anti- EGFR drug after treatment must serve
as a marker of drug response due to the down regulated activity of ERK1/2. (Reference 19, 52). Without a doubt, in
regards to the result, mAbs and EGFR-TKIs did not bring visible changes in
phosphorylated-AKT levels in all cell lines tested.


results are in acquiescent with prior reports which showed the inhibition of reduction
of ERK1/2 from EGFR tyrosine kinase, but does not show no phosphorylation AKT
breast cancer patients with tumour. (Reference
19). Cell prevention of apoptosis and promotion of proliferation can be detected
by signaling pathways such as RAS/MAPK, according to (53)  


According to several of other research
using variety of breast cancer cells, (reference
58) suggested that CDK2 is linked with reduction of cell viability after
treatment of erlotinib. Thus the author discovered that by expressing erlotinib
in EGFR and blocking CDK2 activity caused an increase of sensitivity in TNBC
cell line (reference 58)


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