Amplification of a calcium channel subunit CACNG4 increases breast cancer metastasis

钙通道亚基CACNG4的扩增增加乳腺癌转移

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作者:Nisha Kanwar, Katia Carmine-Simmen, Ranju Nair, Chunjie Wang, Soode Moghadas-Jafari, Heiko Blaser, Danh Tran-Thanh, Dongyu Wang, Peiqi Wang, Jenny Wang, Adrian Pasculescu, Alessandro Datti, Tak Mak, John D Lewis, Susan J Done

Background

Previously, we found that amplification of chromosome 17q24.1-24.2 is associated with lymph node metastasis, tumour size, and lymphovascular invasion in invasive ductal carcinoma. A gene within this amplicon, CACNG4, an L-type voltage-gated calcium channel gamma subunit, is elevated in breast cancers with poor prognosis. Calcium homeostasis is achieved by maintaining low intracellular calcium levels. Altering calcium influx/efflux mechanisms allows tumour cells to maintain homeostasis despite high serum calcium levels often associated with advanced cancer (hypercalcemia) and aberrant calcium signaling.

Methods

In vitro 2-D and 3-D assays, and intracellular calcium influx assays were utilized to measure tumourigenic activity in response to altered CANCG4 levels and calcium channel blockers. A chick-CAM model and mouse model for metastasis confirmed these

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