TY - JOUR
T1 - Overexpression of CEACAM6 promotes migration and invasion of oestrogen-deprived breast cancer cells
AU - Lewis-Wambi, Joan S.
AU - Cunliffe, Heather E.
AU - Kim, Helen R.
AU - Willis, Amanda L.
AU - Jordan, V. Craig
N1 - Funding Information:
We thank Dr. Chris Wambi (Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA) for his valuable comments and critical review of this manuscript. This work was supported by the NIH Career Development Grant 1K01CA120051-01A2; the American Cancer Society Grant IRG-9202714; the Department of Defense Breast Program under award number BC050277 Center of Excellence; Fox Chase Cancer Center Core Grant NIH P30 CA006927; Weg Fund of Fox Chase Cancer Center; and the Hollenbach Family Fund. The views and opinions of the author(s) do not reflect those of the US Army or the Department of Defense.
PY - 2008/8
Y1 - 2008/8
N2 - Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an intercellular adhesion molecule that is overexpressed in a wide variety of human cancers, including colon, breast and lung and is associated with tumourigenesis, tumour cell adhesion, invasion and metastasis. In this study, we showed that CEACAM6 was overexpressed in a panel of oestrogen receptor (ERα)-positive human breast cancer cell lines (MCF-7:5C and MCF-7:2A) that have acquired resistance to oestrogen deprivation, and this overexpression was associated with a more aggressive invasive phenotype in vitro. Expression array analysis revealed that MCF-7:5C and MCF-7:2A cells overexpressed CEACAM6 mRNA by 27-fold and 12-fold, respectively, and were 6-15-times more invasive compared to non-invasive wild-type MCF-7 cells which expressed low levels of CEACAM6. Suppression of CEACAM6 expression using small interfering RNA (siRNA) completely reversed migration and invasion of MCF-7:5C and MCF-7:2A cells and it significantly reduced phosphorylated Akt and c-Src expression in these cells. In conclusion, our findings establish CEACAM6 as a unique mediator of migration and invasion of drug resistant oestrogen-deprived breast cancer cells and suggest that this protein could be an important biomarker of metastasis.
AB - Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an intercellular adhesion molecule that is overexpressed in a wide variety of human cancers, including colon, breast and lung and is associated with tumourigenesis, tumour cell adhesion, invasion and metastasis. In this study, we showed that CEACAM6 was overexpressed in a panel of oestrogen receptor (ERα)-positive human breast cancer cell lines (MCF-7:5C and MCF-7:2A) that have acquired resistance to oestrogen deprivation, and this overexpression was associated with a more aggressive invasive phenotype in vitro. Expression array analysis revealed that MCF-7:5C and MCF-7:2A cells overexpressed CEACAM6 mRNA by 27-fold and 12-fold, respectively, and were 6-15-times more invasive compared to non-invasive wild-type MCF-7 cells which expressed low levels of CEACAM6. Suppression of CEACAM6 expression using small interfering RNA (siRNA) completely reversed migration and invasion of MCF-7:5C and MCF-7:2A cells and it significantly reduced phosphorylated Akt and c-Src expression in these cells. In conclusion, our findings establish CEACAM6 as a unique mediator of migration and invasion of drug resistant oestrogen-deprived breast cancer cells and suggest that this protein could be an important biomarker of metastasis.
KW - Breast cancer
KW - CEACAM6
KW - Endocrine resistance
KW - Invasion and migration
KW - Oestrogen deprivation
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U2 - 10.1016/j.ejca.2008.05.016
DO - 10.1016/j.ejca.2008.05.016
M3 - Article
C2 - 18614350
AN - SCOPUS:48349099494
SN - 0959-8049
VL - 44
SP - 1770
EP - 1779
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 12
ER -