Abstract:
:Osteopontin (OPN) is a phosphorylated glycoprotein that binds to alpha v-containing integrins and is important in malignant transformation and cancer. Previously, we have utilized suppressive subtractive hybridization between mRNAs isolated from the Rama 37 (R37) rat mammary cell line and a subclone rendered invasive and metastatic by stable transfection with an expression vector for OPN to identify RAN GTPase (RAN) as the most overexpressed gene, in addition to that of OPN. Here we show that transfection of noninvasive R37 cells with an expression vector for RAN resulted in increased anchorage-independent growth, cell attachment and invasion through Matrigel in vitro, and metastasis in syngeneic rats. This induction of a malignant phenotype was induced independently of the expression of OPN, and was reversed by specifically reducing the expression of RAN using small-interfering RNAs. By using a combination of mutant protein and inhibitors, it was found that RAN signal transduction occurred through the c-Met receptor and PI3 kinase. This study therefore identifies RAN as a novel effector of OPN-mediated malignant transformation and some of its downstream signaling events in a mammary epithelial model of cancer invasion/metastasis.
journal_name
Oncogenejournal_title
Oncogeneauthors
Kurisetty VV,Johnston PG,Johnston N,Erwin P,Crowe P,Fernig DG,Campbell FC,Anderson IP,Rudland PS,El-Tanani MKdoi
10.1038/onc.2008.325subject
Has Abstractpub_date
2008-12-04 00:00:00pages
7139-49issue
57eissn
0950-9232issn
1476-5594pii
onc2008325journal_volume
27pub_type
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