Abstract Book 2010 - CIMT Annual Meeting

094 Quaglino | Tumor biology & interaction with the immune system
A miRNAs expression profiles during ErbB2 driven mammary
carcinogenesis
Elena Quaglino 1 , Maddalena Arigoni 1 , Elisabetta Ercole 1 , Federica Riccardo 1 , Guido Forni 1 ,
Raffaele Calogero 2 and Federica Cavallo 1
1 Molecular Biotechnology Center (MBC), University of Torino, Italy
2 Bioinformatics and Genomics Unit, Department of Clinical and Biological Science, University of Torino, Italy
MicroRNAs (miRNAs) are noncoding RNAs that
regulate global gene expression. They often act
synergistically to repress target genes, and their
deregulation can contribute to the initiation and
progression of a variety of cancers. In view of the
roles played by miRNAs in cancer progression, we
performed a miRNAs microarray analysis aimed at
identifying the modulation of miRNAs expression
profiles during the progression of authoctonous
mammary carcinomas arising in mice transgenic
for the activated transforming rat ErbB2 oncogene
(BALB-neuT mice). BALB-neuT mice constitute
a suitable cancer-prone model, since inexorably
the females develop an invasive and metastatic
mammary cancer in all of their ten mammary
glands with a step wide pattern and a systemic metastatic
spread similar to that observed in human
mammary cancer. Using Applied Biosystems
Megaplex low density miRNA expression arrays
miRNAs expression signature of diffused atypical
hyperplasia (6 week-old BALB-neuT versus 6 weekold
BALB-c females mammary glands) and invasive
carcinoma (19 week-old BALB-neuT versus 19
week-old BALB-c females mammary glands) were
identified. PCA shows a wide difference in miRNAs
expression between diffused atypical hyperplasia
and invasive carcinoma. Moreover, rank product
analysis allowed the detection of 6 and 4 miRNAs
whose expression is correlated to invasive carcinoma
and to diffused atypical hyperplasia respectively.
Among those that were found to be upregu-
lated in invasive carcinoma miR-135a and miR-135b
were found to be expressed also in several lines
derived from BALB-neuT mammary tumors, suggesting
their role in mammary cancer progression.
By contrast, the expression of miR-741 resulted
undetectable in all the mouse cell lines derived
from BALB-neuT mammary tumors, even if, its expression
was upregulated in mammary BALBneuT
tumors, suggesting its role in the tumor microenvironment
phenotype. Modulation (overexpression
or down-modulation) of miR-135b in breast cancer
cells is under investigation in order to evaluate its
role in the in vivo tumor growth, in vitro matrigel
invasion as well as in vivo lung metastasis formation.
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