Abstract
Cells that are able to localize β-actin mRNA efficiently have decreased metastatic potential. Invasive carcinoma cells derived from primary mammary tumors have reduced levels of an RNA binding protein IMP1/ZBP1/IGF2BP1, required for β-actin mRNA localization. We showed previously that in human breast carcinoma cells in vitro, this protein suppresses invasion. In this work we examined whether its re-expression can suppress breast cancer metastasis in a breast cancer mouse model. We developed a mouse conditionally expressing IMP1-GFP (hereinafter referred to as the IMP1 transgene) specifically in the mammary gland of a PYMT breast cancer mouse. We found that mice conditionally expressing the IMP1 transgene showed little or no metastases to the lungs from the primary tumor in contrast to PYMT mice not expressing IMP1, which uniformly develop metastases at an early stage.
Highlights
Spreading of malignant cells from a primary tumor to other parts of the body is a leading cause of morbidity and mortality in cancer patients and breast cancer metastasis is the leading cause of death in women [1]
In order to evaluate the role of IMP1 in breast cancer metastasis, we crossed the MMTV-PyMT breast cancer mouse model with a conditionally expressing IMP1-GFP transgenic mouse (10)
PyMT is a viral oncogene that when overexpressed in the mouse mammary gland causes widespread proliferation of the mammary epithelium which progresses to multifocal mammary adenocarcinomas and pulmonary metastasis [15]
Summary
Spreading of malignant cells from a primary tumor to other parts of the body is a leading cause of morbidity and mortality in cancer patients and breast cancer metastasis is the leading cause of death in women [1]. Human IMP1 (IGF2 mRNA-binding protein 1) originally cloned as ZBP1 [3], is an important RNAbinding protein important for cell RNA localization, migration, stability, and translational control. It facilitates the localization of β-actin, E-cadherin, α-actinin and ARP2/3 complex mRNAs, which are involved in cellcell connections and focal adhesions [4]. Loss of IMP1 increases the growth ability of metastatic cells and promotes cell motility but decreases persistence [5, 6]. Undirected cell motility is required for tumor cell spreading and subsequent invasion of connective tissue, lymphatic and blood vessels [7]. The expression of IMP1 and the expression of β-catenin are coordinately regulated [8]
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