Lawlor et al. Journal of Experimental & Clinical Cancer Research 2010, 29:81
http://www.jeccr.com/content/29/1/81
Open Access RESEARCH
© 2010 Lawlor et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
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Research
MYEOV (myeloma overexpressed gene) drives colon
cancer cell migration and is regulated by PGE
2
Garrett Lawlor
1
, Peter P Doran
2
, Padraic MacMathuna
1
and David W Murray*
2
Abstract
Introduction: We have previously reported that Myeov (MYEloma OVerexpressed gene) expression is enhanced in
colorectal cancer (CRC) and that it promotes CRC cell proliferation and invasion. The role of Myeov in CRC migration is
unclear. ProstaglandinE2 (PGE
2
) is a known factor in promoting CRC carcinogenesis. The role of PGE
2
in modulating
Myeov expression has also not been defined.
Aim: To assess the role of Myeov expression in CRC cell migration and to evaluate the role of PGE
2
in Myeov bioactivity.
Methods: siRNA mediated Myeov knockdown was achieved in T84 CRC cells. Knockdown was assessed using
quantitative real time PCR. The effect of knockdown on CRC cell migration was assessed using a scratch wound healing
assay. Separately, T84 cells were treated with PGE
2
(0.00025 μ M, 0.1 μ M and 1 μ M) from 30 min to 3 hours and the
effect on Myeov gene expression was assessed using real time PCR.
Results: Myeov knockdown resulted in a significant reduction in CRC cell migration, observable as early as 12 hours (P
< 0.05) with a 39% reduction compared to control at 36 hours (p < 0.01). Myeov expression was enhanced after
treatment with PGE
2
, with the greatest effect seen at 60 mins for all 3 PGE
2
doses. This response was dose dependent
with a 290%, 550% & 1,000% increase in Myeov expression for 0.00025 μ M, 0.1 μ M and 1 μ M PGE
2
respectively.
Conclusion: In addition to promoting CRC proliferation and invasion, our findings indicate that Myeov stimulates CRC
cell migration, and its expression may be PGE
2
dependant.
Introduction
Colorectal cancer is a heterogeneous disease arising from
a complex series of molecular changes [1]. In 1990,
Fearon and Vogelstein described the molecular basis of
colorectal cancer as a multi-step model of carcinogenesis
[2]. The model describes the accumulation of genetic
events, each conferring a selective growth advantage to
an affected colon cell, including inactivation of tumour
suppressor genes and activation of oncogenes.
Using a bioinformatics approach we have identified
genes with enhanced expression in colorectal cancer tis-
sue [3,4]. Myeov, (MYEloma OVerexpressed gene) was
initially noted for its association with a subset of multiple
myeloma cell lines [4,5] and it has also been implicated in
oesophageal squamous cell carcinomas [6] and breast
cancer [7]. Myeov is co-amplified with cyclin D1, a
known oncogene [5]. We have previously shown Myeov
to play a role in gastric cancer cell proliferation and inva-
sion [3].
Our group has demonstrated a role for Myeov in the
pathogenesis of colorectal cancer (CRC), noting a 20-fold
increase in Myeov expression in CRC in comparison with
normal colorectal tissue [3]. We have also confirmed that
Myeov is upregulated in CRC ex vivo using tissue from
normal colonic mucosa, adenomas, and carcinomas [3].
Our In vitro RNA interference/knockdown studies, in
which Myeov expression was inhibited, revealed a role for
Myeov in driving CRC cell proliferation and invasion.
However, the role of Myeov expression in CRC cell
migration has not been elucidated. We hypothesise,
because of its established role in tumour cell invasion,
that Myeov is also important for tumour cell migration.
The mechanism underlying Myeov expression remains
unclear.
* Correspondence: dmurray@mater.ie
2
UCD Clinical Research Centre, UCD School of Medicine & Medical Sciences,
UCD, 21 Nelson St, Dublin 7, Ireland
Full list of author information is available at the end of the article