Cristian Gonzalez

English 363

GATA3 and its Effects on Cancer Metastasis and Cell Differentiation

Target Audience: Public with some basic understanding in the sciences and medical advancements

differentiation and in result decreases

Introduction

metastasis, as shown in figure 2 (Chou,

2013).

The more technology advances, the

greater understanding of cancer we have.
Thanks to the increased public awareness of
cancer, more is known about cell
differentiation and the reduction of
metastasis. Our own body may someday aid
in the elimination of aggressive cancer on its
own. GATA3 is a newly discovered
transcription factor found in the breast that
helps maintain luminal structure in cells,
which helps prevent metastasis of breast
cancer and tumor growth in the area.
Whenever there is a presence of this
transcription factor or activator, it can either
inhibit or regulate genes attributed to
promote the growth or metastasis of breast
and lung cancer (Dydensborg, 2009).
GATA3 also acts as an activator for the
promoter miR-29b and increases cell

cancer.ucsf.edu
Figure 2
Common pathways taken by GATA3 to reduce
metastasis.

GATA3 has been found to have the same

effects in bladder cancer but not all the time
(Li, 2014). Moreover, when GATA3 is
found in bladder cancer, it takes the same
pathway to promote expression of antimetastatic genes and inhibits any other
activators from expressing their prometastatic genes. This review will focus on
the mechanisms of GATA3 and how it is
able to suppress metastasis in both tumor
and cancer cells.

Results
GATA3 on breast cancer metastasis
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Cristian Gonzalez
English 363

There is a correlation between high

an electrophoresis gel run (Dydensborg,

GATA3 expression and low metastases

2009). The gel run helps by labeling a

amongst cancer patients. GATA3 has

specific RNA fragment and seeing if it

specific features that allow it to function as

appears after the gel is done. The

an inhibitor and target genes that promote

aggressiveness level is important because it

breast cancer metastases to the lungs or

determines how metastatic a cancer can be

anywhere else in the body (Dydensborg,

and how fast it can spread. Figure 2 has an

2009). In addition with the statement,

example of how cancer cells and normal

several experiments with cancer cell lines

cells would differ generally.

from patients show a control with no

GATA3 and a treatment with GATA3 and

www.dayasriome.bid

Figure

1.

how they differ genetically and physically.

Patients that had high expression of this
transcription factor were found to have less

Different phenotypic differences

between a
breast cancer cell and a normal cell of the same kind.

aggressive cells and a greater number of

differentiated cells than the patients that had
a lower expression. Differentiation in cells is
important and a positive feature because it
means the cell is working properly and not
replicating in out of the ordinary amounts
(Yan, 2010). The data was obtained by
getting cell linings from the patient where
the cancer was present and then conducting

In another research with around 80

individuals, patients with higher levels of
GATA3 were more metastasis free than the
patients with lower levels of GATA3
(Dydensborg, 2009). A closer look at the
molecular level using PCR and Western
Blotting showed that GATA3 was
responsible for the upregulation of certain

Cristian Gonzalez
English 363

genes and the inhibition of others. PCR is

throughout time in the cancer stages, miR-

used to identify different RNA fragments

29b, along with others in the miR family

that you are looking for and Western

such as miR-128 that were expressed less,

Blotting tracks the protein production and

was found to be active whenever GATA3

expressions, that way you are able to

was expressed (Chou, 2013)(Bockhorn,

visualize the proteins being targeted by

2014). Microarray data was able to confirm

GATA3. Interestingly, GATA3 was

that miR-29b expression levels were

responsible for activating genes, such as

upregulated when GATA3 was present in the

PAEP and DLC1, which created more

cancer cell. It was also absent whenever

inhibitors that would prevent or at least

GATA3 was absent in the cancer cell. MiR-

reduce the aggressiveness of breast cancer

29b is a type of mRNA promoter that is

and therefore decrease its metastasis

active whenever GATA3 is attached to it

(Dydensborg, 2009). In response to the

since it seems that GATA3 is its activator.

increase of inhibitors, the regulation of pro-

Usually when there is no presence of

metastatic genes such as ID1, LY6E,

GATA3 in the cell, miR-29b is inhibited by

KRTHB1 and RATTES3 were down

TGF-beta, which is another promoter found

regulated. These results were obtained from

to bind to miR-29b. Thus by removing the

data found by RT-PCR, which analyzes

inhibitor TGF-beta and then binding to miR-

RNA sequences of choice.

29b, GATA3 activates miR-29b which

GATA3 on breast cancer and miR-29

decreases metastasis and cancer/tumor

growth (Chou, 2013). GATA3 is then

After multiple experiments to find

responsible for two different actions that
genes that seemed to have a relationship
results in the differentiation of cells, the first
with GATA3 and analyzing gene expressions
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being that it activates the miR-29b

cell differentiation. This whole pathway

expression for reduced metastasis and the

would be prevented if GATA3 binds to miR-

other by inhibiting TGF-beta, a known pro-

29, not allowing for the binding of TGF-beta

metastatic promoter, from binding to miR-

and therefore activating the differentiation

29b.

expression of the miR-29b and GATA3

MiR-29b was also found to promote

luminal differentiation, which means that the

compound.
A family MMP genes were also

tumor and cancer cells began to become less

down regulated by the over expression of

aggressive and less metastatic. There were

GATA3, such as MMP-2, MMP-9, and

two important genes, CD49 and CD29,

MMP-10 (Mohamed, 2011). These genes

which the microarray data showed were

are responsible for cell degradation because

down regulated when in presence of

they chew other cells, making them

GATA3. CD49 and CD29 are present when

dangerous in cancer. When MMP genes are

cell differentiation is low and cell metastasis

active in cancer cells, they multiply and

is high, meaning that there is less expression

destroy other cells nearby that may still have

of miR-29b (Chou, 2013). Conclusions were

been healthy.

drawn by comparing expressions of RNA

Loss of GATA3 in breast and bladder cancer

between cells that had GATA3 present and

GATA3 was found in bladder cancer
cells that did not, TGF-beta directly
recently but it does not take on the same
upregulates the expression of CD49 and
pathways as described earlier in the review.
CD29 by inhibiting miR-29b. The
To further test what role GATA3 played in
inhibition of miR-29b allows for CD49 and
the bladder, cancer cell lines were obtained
CD29 to become expressed and decrease
from different patients and made sure
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English 363

GATA3 was being expressed at the time (Li,

and GATA3 had a similar outcome to that of

2014). Since GATA3 was already active and

the removal of GATA3 in breast cancer. The

doing its job in reducing growth and spread

genes activated by the removal of GATA3 in

of the cancer, an inhibitor would be

both bladder and breast cancer may be

introduced to see what effect it would have

different but it proves that GATA3 is a key

on the bladder cancer if no GATA3 were

player in keeping pro-metastatic genes

present (Li, 2014). After using a silencing

inhibited.

gene to inhibit the activation of GATA3, it

Conclusion

was observed that the cancer cell migration

GATA3 was found to be important in
increased slightly, establishing that GATA3
the reduction of cell metastasis in breast and
played a small role in preventing or slowing
bladder cancer by inhibition and regulation.
the metastatic capabilities of the cancer.
There were several pathways that GATA3
Looking at the molecular level, an RT-PCR
could take in order to down regulation the
was conducted to see if any changes in gene
activity and expression of pro-metastatic
expression occurred when the GATA3 was
genes, such as by binding to miR-29b and
inhibited. MMP-2 and MMP-9 expression
promoting cell differentiation which
and activity increased in the absence of
decreases metastatic characteristics. GATA3
GATA3 (Li, 2014).
could also inhibit pro-metastatic genes, like
MMP-2 and MMP-9 have pro-

MMP-9/MMP-2, itself, like shown in

metastatic capabilities and promote quicker

bladder cancer. Though the methods taken

cell migration. Further analyzation of the

by GATA3 may vary depending on where

RT-PCR test before and after the removal of

the cancer is located or how much of it is

GATA3 showed that the MMP-2/MMP-9

present, GATA3 has shown through research

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Cristian Gonzalez
English 363

that it is able to work as an important

transcription factor to help promote cell

differentiation and decrease cell metastasis.

References
1. Bockhorn, J., Prat, A., Chang, Y., Liu, X., Huang, S., Shang, M., Liu, H. (2014).
Differentiation and Loss of Malignant Character of Spontaneous Pulmonary
Metastases in Patient-Derived Breast Cancer Models. Cancer Research, 74(24),
7406-7417.

2. Chou, J., Lin, J., Brenot, A. , Kim, J. , Provot, S., et al. (2013). Gata3 suppresses
metastasis and modulates the tumor microenvironment by regulating microrna-29b
expression. Nature Cell Biology, 15(2), 201-213.

3. Dydensborg, A., Rose, A., Wilson, B., Grot, D., Paquet, M., et al. (2009). Gata3
inhibits breast cancer growth and pulmonary breast cancer
metastasis. Oncogene, 28(29), 2634-2642.
4. Li, Y., Ishiguro, H., Kawahara, T., Kashiwagi, E. , Izumi, K. , et al. (2014). Loss of
gata3 in bladder cancer promotes cell migration and invasion. Cancer Biology &
Therapy, 15(4), 428-435.

5. Mohamed E. (2011, October 5). MMP-10/Stromelysin-2 Promotes Invasion of Head

and Neck Cancer. Retrieved from http://journals.plos.org/plosone/article?
id=10.1371/journal.pone.0025438
6. Yan, W., Cao, Q., Arenas, R., Bentley, B., & Shao, R. (2010). Gata3 inhibits breast
cancer metastasis through the reversal of epithelial-mesenchymal transition. Journal
of Biological Chemistry, 285(18), 14042-14051.

I used the guidelines presented by Oncogene on

http://www.nature.com/onc/onc_new_gta.pdf.
Due to page limitations though, I was not able to dedicate a whole section for materials
and methods.