2015, Volume 31, Number 1, Page(s) 009-015
Metastasis-Associated Protein 1 Expression in Oral Squamous Cell Carcinomas: Correlation with Metastasis and Angiogenesis
Azadeh ANDISHEHTADBIR1, Ali Dehghani NAJVANI1, Soheil PARDIS1, Zohreh Jafari ASHKAVANDI1, Mohammad Javad ASHRAF2, Bijan KHADEMI3, Fereshteh KAMALI1
1Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, SHIRAZ, IRAN
2Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, SHIRAZ, IRAN
3Department of Otolaryngology, Khalili Hospital, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, SHIRAZ, IRAN
Keywords: MTA-1 protein, Squamous cell carcinoma, Immunohistochemistry, Metastasis, Head and neck neoplasms
Metastasis-associated protein 1 (MTA1) has been associated
with poor prognosis in several carcinomas. Recent investigation has
found that in different tumors, MTA1 protein significantly correlates
with tumor angiogenesis, suggesting that MTA1 may be a possible
angiogenesis-promoting molecule in malignant tumors. Thus, the
current study was performed to determine the role of MTA1 protein
in the biological behavior of oral squamous cell carcinoma and its
relation with tumor angiogenesis.
Material and Method: In this study, 44 oral squamous cell carcinomas
and 15 normal epitheliums were reviewed by IHC staining for MTA1
Results: Frequency of MTA1 expression in SCCs was recorded as
97.7%, which was significantly higher than that of the control group
(33.3%). Mean percentage of MTA1 expression in oral squamous
cell carcinomas was 76.88 ± 25.33% which was significantly higher
than that of the control group (22.81 ±10.83). Our data showed a
correlation between MTA1 expression with lymph node metastasis,
tumor size and, stage. Evaluation of the correlation between MTA1
protein expression and micro vessel density showed that high micro
vessel density was detected more frequently in tumors with MTA1
protein overexpression than in those without overexpression.
Conclusion: In the present study, high expression of the MTA1 protein
was seen in oral squamous cell carcinoma, and was closely associated
with tumor progression and increased tumor angiogenesis. The
findings may indicate that MTA1 protein has clinical potentials as
a useful indicator of progressive phenotype, a promising prognostic
predictor to identify patients with poor prognosis and may be a
potential novel therapeutic target of anti-angiogenesis for patients
with oral squamous cell carcinoma.
Oral cancer is the eleventh most common cancer in the
world, and squamous cell carcinoma (SCC) constitutes
approximately 94% of all oral malignancies. The overall
5-year survival rate for intra oral carcinoma ranges from
27% to 68% and a great majority of deaths occur within
the first 5 years1
. Equivocal results are shown for various
molecular markers associated with carcinoma, and for
determining patient prognosis. However, considerable
differences in survival exist among patients with the same
pathologic stage, so it is not sufficient to accurately predict
a patient’s prognosis on the basis of the current staging
. Therefore, it is necessary to find novel
biomarkers that could be used as predictors so that the
conventional staging system risk stratification can be
. These biomarkers can help us to find patients
who will benefit from adjuvant therapy with poor prognosis
Metastasis is the result of complicated events including
factors such as those important for the separation of
neoplastic cells from the initial tumor, penetration into the
blood and lymphatic, arrest at remote sites by adhesion to
endothelial cells, extravasation, induction of angiogenesis,
evasion of host antitumor responses, and growth at
metastasis sites6. As molecular biology has improved,
novel molecules involved in carcinogenesis and tumor
progression have been discovered. Metastasis-associated
genes (MTA) are a recently found group of tumor
progression-related genes with three different members:
MTA1, MTA2 and MTA37.
Among them, metastasis-associated protein 1 (MTA1)
is a component of the nucleosome remodeling and
histone deacetylation (NURD) complex, and is involved
in remodeling of adenosine triphosphate-dependent
chromatin and function of histone deacetylase8. The
MTA1 protein functions in conjunction with other
components of NURD to mediate transcriptional repression
as it facilitates the association of repressor molecules
with the chromatin9,10. Few studies have shown that
MTA1 has an effect on invasiveness of oral squamous
cell carcinoma (OSCC), although cancer progression and
metastatic state are thought to be affected by the great
invasive potential of cancer cells11.
Tumor angiogenesis occurs in the early stage during cancer
pathogenesis and is basically required for carcinogenesis,
progression, and metastasis of malignant tumors12,13.
Micro vascular density (MVD) is a good predictor of
angiogenesis. Since 1991, many markers have been introduced to stain the vessels. However, none of them can
distinguish between neovasculature and preexisting ones
except CD10514. CD105, also known as endoglin, is a
good marker for measuring MVD15,16. It is a 180KDa
homotypedipolymer glycoprotein in the endothelial cell
membrane that modulates responses to TGFβ14. Its gene
is located on chromosome 9q3417.
Recent investigations have found that in different
tumors, MTA1 protein significantly correlates with
tumor angiogenesis, suggesting MTA1 may be a possible
angiogenesis-promoting molecule in malignant tumors4,14,15,16,17. Accordingly, the present study aimed to
determine the role of MTA1 protein in the biologic behavior
of oral SCC and its relation with tumor angiogenesis.
In this cross-sectional study, the specimen from 44 patients
with OSCC (29 males and 15 females) with the mean age
of 54.47 (range 35-81) from the archives of Khalili Hospital
between 2008 and 2012 were studied. The control group
consisted of 15 cases of normal oral epithelium.
Immunohistochemical (IHC) staining and analysis: First,
H&E slides of available blocks were reviewed and then
cases with definite diagnosis and adequate cellular tissue
were selected for immunohistochemical staining (IHC).
IHC staining was performed using the Envision Labeled
Peroxidase System (DAKO, Carpentaria, CA, USA). All
the samples were fixed at 10% buffered formalin and were
embedded in paraffin. Sections with 4μ thickness were
prepared, deparaffinized in xylene, rehydrated in graded
alcohol and were washed with distilled water. Antigen
retrieval for MTA1 and CD105 was performed using
DAKO estimation, target retrieval solution with PH = 9,
for 20 minutes. Internal peroxidase activity was inhibited
by 3% H2O2.
Tissue sections were then incubated for 30 minutes with
the anti-MTA1 monoclonal antibody (mouse, Abcam
Corporation, ab64214, UK) and anti-CD105 monoclonal
antibody (mouse, novocastra Corporation, NCL_CD105,
Germany) at 1/10 dilution. Brown cytoplasmic staining
for CD105 and both cytoplasmic and nuclear staining for
MTA1 was considered as positive. Omission of the primary
antibody was employed as negative control, while liver tissue
was used as positive control for CD105 and an esophageal
cancer tissue known to overexpress MTA1 protein was used
as positive control for MTA1 protein staining.
Intratumoral micro vessel density was quantified according
to a recent consensus statement18. Briefly, in an optical microscope, hotspot areas for CD105 expression with
discrete blood vessels were initially identified by scanning
the entire tumor at low power (x40). The number of CD105
highlighted vessels in 10 of these areas was then counted
with high-power magnification (x400).
For MTA1 protein assessment, immunoreactivity was
evaluated using a semiquantitative scoring system for both
staining intensity (0, negative staining; 1, weak staining;
2, moderate staining; 3, intense staining) and percentage of
positively stained cancer cells (0;0-5%; 1;6-25%; 2;26-50%;
3;51-75%; 4; ≥76%). The final staining score was the sum of
the scores of staining intensity and percentage of positive
cells, and was further graded as follows: (0), 0-1; (1), 2-3;
(2), 4-5; (3), 6-7. Tumors with the final staining score ≥ 4
were defined as overexpressing MTA1 protein, a system
that had been validated in previous studies19.
Statistical analysis: Student’s t test, the Mann-Whitney test,
chi_square test, Spearman’s correlation coefficient test and
Pearson’s correlation coefficient test were used to compare
the results between the two groups and the relation with
clinic-pathologic features such as age, sex, tumor size,
histopathological grade, lymph node metastasis and tumor
stage. We used the SPSS15 software to statistically analyze
the data. A P-value ≤ 0.05 was considered significant in all
the statistical analyses.
|Expression of MTA1 in oral cancer:
In the present study,
MTA1 was expressed in both the cytoplasm and nucleus
of the tumor cells; however, in control cases, its expression
was only cytoplasmic (Figure 1
). Frequency of MTA1
expression in OSCCs was recorded as 97.7%, which was
significantly higher than that of the control group (33.3%)
(p<0.001). Mean percentage of MTA1 expression in OSCCs
was 76.88 ± 25.33 and was significantly higher than that of
the control group (22.81 ±10. 83) (p<0.001).
Click Here to Zoom
|Figure 1: Cytoplasmic MTA-1 expression in normal oral mucosa
Click Here to Zoom
|Figure 2: Intense cytoplasmic MTA-1 expression in oral squamous
cell carcinoma (MTA-1; x200).
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|Figure 3: Nuclear and cytoplasmic MTA-1 expression in oral
squamous cell carcinoma (MTA-1; x200).
Our data showed a positive correlation between MTA1
expression and stage (r= 0.6, p<0. 001) (Table I). MTA1
expression was significantly higher in node positive
patients (Median: 2) than node negative cases (Median: 0),
(p<0.001). MTA1 expression was not related to tumor size
and grade (p>0.05).
Click Here to Zoom
|Table I: Correlation of clinicopathological data with MTA1¹ expression and MVD² of the patients included in this study
The mean CD105-MVD value was significantly higher in
tumoral tissue (20.02±8.03) when compared to normal
tissues (8.67±1.75) (p<0.001). CD105 MVD in OSCC was
associated with lymph node status (p=0. 005) and clinical
stage (p<0. 001), but it was not related to age, sex, tumor
size and grade (p>0.05).
Correlation of MTA1 protein with MVD: Evaluation of the
correlation between MTA1 protein expression and MVD
showed that high MVD was detected more frequently in
tumors with MTA1 overexpression than in those without
overexpression (Figure 4,5) (r=0. 5, p<0. 001).
Click Here to Zoom
|Figure 4: High CD105-MVD in oral squamous cell carcinoma
Click Here to Zoom
|Figure 5: Correlation between MTA score and MVD (r=0.5,
Oral squamous cell carcinoma (OSCC) forms nearly 3% of
all malignancies in the United States and about 28900 new
cases of oral cancer are noticed yearly, resulting in 7400
. Prognosis of patients with OSCC is primarily
determined by the stage of disease at the time of diagnosis.
However, the staging system is not sufficient for the
prediction of prognosis21,22
. Thus, to optimize treatment
for oral cancer patients, new biomarkers may be employed
as an adjunct to the staging system that could be used as a
possible therapeutic target or a prognostic predictor23
Our study proved that the CD105-MVD value was
significantly higher in OSCCs than normal tissue. It was in line with previous studies24-27 and verified that
CD105 is expressed more in tumoral tissues and may have
a major role in tumor development. We also observed a
positive relation between CD105 expression and lymph
node metastasis. This finding is compatible with previous
investigations28-32 and suggests that the marker can be
helpful in predicting the possibility of metastasis.
MTA1, the basic member of the MTA family was primarily
recognized via differential screening of the cDNA Library
from rat metastatic breast tumors as an upregulated gene33-35. MTA1 upregulation was seen in various human
cancers and shown to be involved in tumorigenesis, tumor
invasion, and metastasis36,37. So far, there has only
been one clinical study of MTA1 expression in OSCCs; it
has reported that MTA1 expression in control tissues was
significantly lower than carcinomas, and showed MTA1
protein production was strongly associated with cancer
cell invasion, and there was clinically a correlation between
lymph node metastasis and MTA1 protein production. The authors stated that MTA1 overexpression in OSCC may
lead to increased invasive ability and lymph node metastasis11.
In the present study, we found a relationship between
MTA1 expression and clinicopathological factors such
as metastasis to lymph node and stage. The obtained
result indicates that MTA1 might play a role in tumor
progression and is consistent with other studies4,11,14.
The mechanism by which MTA1 protein contributes to the
progressive potential of OSCC has not been investigated;
however, evidence has shown that MTA1 protein is
significantly correlated with tumor angiogenesis, and MTA1
protein contributes to angiogenesis through regulating hypoxia-inducible factor-1α (HIF-1α), suggesting that
MTA1 may be a possible angiogenesis-promoting molecule
in malignant tumors16,17.
Shu_Hai Li et al. reported that overexpression of the MTA1
protein is common in esophageal SCC (ESCC), and is closely
related to tumor progression, increased tumor angiogenesis,
and poor survival. These results reveal that MTA1 protein
can be a useful indicator of progressive phenotype, a
promising prognostic predictor to identify patients with
poor prognosis, and a potential novel therapeutic target of
antiangiogenesis for patients with ESCC4.
In another study, Shu-hai Li et al. found that MTA1 protein
overexpression was common in early-stage non small cell
lung cancer and was correlated with tumor angiogenesis
and relapse. Moreover, MTA1 protein overexpression could
affect patient survival and was an independent prognostic
factor for disease-free, overall, and disease specific survival18.
However, to the best of the authors’ knowledge, the
present study is the first clinical report to investigate
the role of MTA1 protein in relation to angiogenesis in
OSCCs. The findings of our study showed that MTA1
protein overexpression was common in OSCC tissues and
significantly associated with increased angiogenic activity
suggesting that MTA1 protein might promote tumor
progression and development of aggressive phenotypes by
the induction of tumor angiogenesis but further studies
is recommended to investigate the relationship of these
markers with the more accurate method for proving
this finding. The mechanism by which MTA1 protein
contributes to the angiogenic potential of cancer cells and
formation of new tumor microvessels is unclear and still
needs to be further investigated.
Mazudmar et al. reported in general, the MTA proteins
contain basic nuclear localization signals and are
predominantly localized in the nucleus. Analysis of various
mouse tissues suggested that variable, but easily detectable,
levels of MTA1 protein are present in multiple organ
systems including lung, liver, kidney, heart and testes, thus
suggesting a physiologic function of MTA1 in normal
Manavathi and Kumar have documented the predominantly
nuclear localization of MTA1 in various cancerous tissues,
including ovarian, lung, gastric and colorectal cancers39.
However, Moon et al. showed in human hepatocarcinoma
(HCC) cells, MTA1 localizes to both the nucleus and
cytoplasmic compartments19. Li et al. also reported both
cytoplasmic and nuclear expression of MTA1 in NSCLC18. In our study, we have seen MTA1 expression in both
the nucleus and cytoplasm, which was consistent with the
results obtained by Moon et al.19 and Li et al.18.
The expression of MTA family members is not restricted
to cancer cells, but one of the most important issues in
MTA family research is that little information about the
physiological functions and underlying mechanisms in
normal cells is available. According to the recent researches
and the findings that MTA1 is a master co-regulatory
molecule, it is quite possible that MTA1 deregulation may
interfere in other human diseases than cancer.
Because MTA family members were found in distinct
subcellular compartments, it is important to understand
the underlying biochemical basis of differential sub cellular
localization and whether it is further affected by extracellular
signals or not. Furthermore, to fully appreciate the master
regulatory function of MTA1 (or other MTA family
members), it is of paramount importance to understand the
nature of the biochemical switch responsible for corepressor
versus coactivator activity of MTA1. In addition to further
researching the cellular functions of MTA1, there is a clear
need to intensify research connecting various domains
of MTA1 (or other MTA family members) with specific
In conclusion; In this study, high expression of the MTA1
protein was seen in OSCC, and was closely associated with
tumor progression and increased tumor angiogenesis.
These findings may indicate that MTA1 protein has clinical
potentials as a useful indicator of progressive phenotype,
a promising prognostic predictor to identify patients with
poor prognosis and may be a potential novel therapeutic
target of anti-angiogenesis for patients with OSCC, but to
confirm this relationship in the context of MTA1 expression
leading to enhanced angiogenesis, further experimentation
using OSCC cell lines overexpressing or silencing MTA1
and examining the incidence of angiogenesis should be
Acknowledgements: This manuscript is based on the postgraduate
thesis of Dr. Fereshteh Kamali. The authors are
also grateful to Dr. M. Vossoughi from Dental Research
Development Center of the Dental School, for the statistical
Funding Source: This research program was supported by
Vice-Chancellor of Shiraz University of Medical Sciences
1) Neville BW, Damm DD, Allen CM, Bouqout JE: Oral and
maxillofacial pathology. 3rd ed. Philadelphia: Saunders; 2002. 317-36.
2) Ghanta KS, Li DQ, Eswaran J, Kumar R. Gene profiling of MTA1
identifies novel gene targets and functions. PloS One. 2011;6:
3) Law S, Kwong DL, Kwok KF, Wong KH, Chu KM, Sham JS, Wong
J. Improvement in treatment results and long-term survival of
patients with esophageal cancer: Impact of chemoradiation
and change in treatment strategy. Ann Surg. 2003;238:339-47;
4) Li SH, Tian H, Yue WM, Li L, Gao C, Li WJ, Hu WS, Hao B.
Metastasis-associated protein 1 nuclear expression is closely
associated with tumor progression and angiogenesis in patients
with esophageal squamous cell cancer. World J Surg. 2012;
5) Shih CH, Ozawa S, Ando N, Ueda M, Kitajima M. Vascular
endothelial growth factor expression predicts outcome and lymph
node metastasis in squamous cell carcinoma of the esophagus.
Clin Cancer Res. 2000;6:1161-8.
6) Toh Y, Oki E, Oda S, Tokunaga E, Ohno S, Maehara Y,
Nicolson GL, Sugimachi K. Overexpression of the MTA1 gene
in gastrointestinal carcinomas: correlation with invasion and
metastasis. Int J Cancer. 1997; 74:459-63.
7) Toh Y, Nicolson GL. The role of the MTA family and their
encoded proteins in human cancers: Molecular functions and
clinical implications. Cli Exp Metastasis. 2009;26:215-27.
8) Kidd M, Modlin IM, Mane SM, Camp RL, Eick G, Latich I. The
role of genetic markers-NA P1L1, MAGE-D2, and MTA1-in
defining small-intestinal carcinoid neoplasia. Ann Surg Oncol.
9) N icolson GL, Nawa A, Toh Y, Taniguchi S, Nishimori K, Moustafa
A. Tumor metastasis-associated human MTA1 gene and its
MTA1 protein product: Role in epithelial cancer cell invasion,
proliferation and nuclear regulation. Clin Exp Metastasis.
10) Yan C, Wang H, Toh Y, Boyd DD. Repression of 92-kDa type
IV collagenase expression by MTA1 is mediated through direct
interactions with the promoter via a mechanism, which is both
dependent on and independent of histone deacetylation. J Biol
11) Kawasaki G, Yanamoto S, Yoshitomi I, Yamada S, Mizuno A.
Overexpression of metastasis-associated MTA1 in oral squamous
cell carcinomas: Correlation with metastasis and invasion. Int J
Oral Maxillofac Surg. 2008;37:1039-46.
12) Eskens FA. Angiogenesis inhibitors in clinical development;
Where are we now and where are we going? Br J Cancer. 2004;90:
13) Kerbel R, Folkman J. Clinical translation of angiogenesis
inhibitors. Nat Rev Cancer. 2002;2:727-39.
14) Florence ME, Massuda JY, Bröcker EB, Metze K, Cintra ML, Souza
EM. Angiogenesis in the progression of cutaneous squamous
cell carcinoma: An immunohistochemical study of endothelial
markers. Clinics (Sao Paulo). 2011;66:465-8.
15) Marioni G, Ottaviano G, Giacomelli L, Staffieri C, Casarotti-
Todeschini S, Bonandini E Staffieri A, Blandamura S. CD105-
assessed micro-vessel density is associated with malignancy
recurrence in laryngeal squamous cell carcinoma. Eur J Surg
16) Z vrko E, Mikic A, Vuckovic L. Clinicopathologic significance
of CD105-assessed microvessel density in glottic laryngeal
squamous cell carcinoma. Auris Nasus Larynx. 2010;37:77-83.
17) Li SL, Gao DL, Zhao ZH, Liu ZW, Zhao QM, Yu JX, Chen KS,
Zhang YH. Correlation of matrix metalloproteinase suppressor
genes RECK, VEGF, and CD105 with angiogenesis and biological
behavior in esophageal squamous cell carcinoma. World J
18) Li SH, Tian H, Yue WM, Li L, Li WJ, Chen ZT, Hu WS, Zhu
YC, Qi L. Overexpression of metastasis-associated protein 1
is significantly correlated with tumor angiogenesis and poor
survival in patients with early-stage non-small cell lung cancer.
Ann Surg Oncol. 2011;18:2048-56.
19) Moon WS, Chang K, Tarnawski AS. Overexpression of metastatic
tumor antigen 1 in hepatocellular carcinoma: Relationship to
vascular invasion and estrogen receptor-alpha. Human Pathol.
20) Jang KS, Paik SS, Chung H, Oh YH, Kong G. MTA1 overexpression
correlates significantly with tumor grade and angiogenesis in
human breast cancers. Cancer Sci. 2006; 97:374-9.
21) Moon HE, Cheon H, Chun KH, Lee SK, Kim YS, Jung BK, Park
JA, Kim SH, Jeong JW, Lee MS. Metastasis-associated protein 1
enhances angiogenesis by stabilization of HIF-1alpha. Oncology
22) Vermeulen PB, Gasparini G, Fox SB, Colpaert C, Marson LP,
Gion M, Beliën JA, de Waal RM, Van Marck E, Magnani E,
Weidner N, Harris AL, Dirix LY. Second international consensus
on the methodology and criteria of evaluation of angiogenesis
quantification in solid human tumours. Eur J Cancer.
23) Li SH, Wang Z, Liu XY. Metastasis-associated protein 1 (MTA1)
overexpression is closely associated with shorter disease-free
interval after complete resection of histologically node-negative
esophageal cancer. World J Surg. 2009;33:1876-81.
24) Margaritescu C, Simionescu C, Mogoanta L, Badea P, Pirici D,
Stepan A, Ciurea R. Endoglin (CD105) and microvessel density
in oral squamous cell carcinoma. Rom J Morphol Embryol.
25) Schimming R, Marme D. Endoglin (CD105) expression
in squamous cell carcinoma of the oral cavity. Head Neck.
26) Eshghyar N, Mohammadi N, Rahrotaban S, Motahhary P, Vahedi
Vaez SM. Endoglin (CD105) positive microvessel density and
its relationship with lymph node metastasis in squamous cell
carcinoma of the tongue. Arch Iran Med. 2011; 14:276-80.
27) Margaritescu C, Pirici D, Stinga A, Simionescu C, Raica
M, Mogoanta L, Stepan A, Ribatti D. VEGF expression
and angiogenesis in oral squamous cell carcinoma: An
immunohistochemical and morphometric study. Clin Exp Med.
28) Miyahara M, Tanuma J, Sugihara K, Semba I. Tumor
lymphangiogenesis correlates with lymph node metastasis and
clinicopathologic parameters in oral squamous cell carcinoma.
29) Chien CY, Su CY, Hwang CF, Chuang HC, Hsiao YC, Wu SL,
Huang CC. Clinicopathologic significance of CD105 expression
in squamous cell carcinoma of the hypopharynx. Head Neck.
30) Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance
of vascular endothelial growth factor immunohistochemical
expression in head and neck squamous cell carcinoma: A metaanalysis.
Clin Cancer Res. 2005;11:1434-40.
31) Martone T, Rosso P, Albera R, Migliaretti G, Fraire F, Pignataro
L, Pruneri G, Bellone G, Cortesina G. Prognostic relevance of
CD105+ microvessel density in HNSCC patient outcome. Oral
32) Kademani D. Oral cancer. Mayo Clin Pro. 2007;82:878-87.
33) Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, Yuan A, Cheng
CL, Wang CH, Terng HJ, Kao SF, Chan WK, Li HN, Liu CC,
Singh S, Chen WJ, Chen JJ, Yang PC. A five-gene signature and
clinical outcome in non-small-cell lung cancer. N Engl J Med.
34) D’Amico TA. Angiogenesis in non-small cell lung cancer. Semin
Thorac Cardiovasc Surg. 2004;16:13-8.
35) Manavathi B, Singh K, Kumar R. MTA family of coregulators
in nuclear receptor biology and pathology. Nucl Recept Signal.
36) Guo NL, Wan YW, Tosun K, Lin H, Msiska Z, Flynn DC, Remick
SC, Vallyathan V, Dowlati A, Shi X, Castranova V, Beer DG, Qian
Y. Confirmation of gene expression-based prediction of survival
in non-small cell lung cancer. Clin Cancer Res. 2008;14:8213-20.
37) Denslow SA, Wade PA. The human Mi-2/NuRD complex and
gene regulation. Oncogene. 2007;26:5433-8.
38) Mazumdar A, Wang RA , Mishra SK, Adam L, Bagheri-Yarmand
R, Mandal M, Vadlamudi RK, Kumar R. Transcriptional
repression of oestrogen receptor by metastasis-associated protein
1 corepressor. Nat Cell Biol. 2001;3:30-7.
39) Manavathi B, Kumar R. Metastasis tumor antigens, an emerging
family of multifaceted master coregulators. J Biol Chem.