Overexpression of CEACAM6 promotes migration and invasion of oestrogen-deprived breast cancer cells

Abstract

Carcinocinoembryonic 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 the present 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 to 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 E-cadherin, Akt, and 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.

The Selective Estrogen Receptor Modulator Bazedoxifene Inhibits Hormone-Independent Breast Cancer Cell Growth and Down-Regulates Estrogen Receptor α and Cyclin D1

“…Aliquots of the cDNA were combined with the SYBR green kit (Superarray) and primers and assayed in triplicate by quantitative PCR over 40 cycles using a GeneAmp 5700 Sequence detection system (Applied Biosystems, Foster City, CA) as described previously (Lewis et al, 2005a). Quantitation was done using the comparative CT method with 18S rRNA as the normalization gene, as described previously (Lewis-Wambi et al, 2008a). PCR primer sequences used were as follow: ER␣ forward, 5Ј-GGAGGGCAGGGGTGAA-3Ј; ER␣ reverse, 5Ј-GGCCAG-GCTGTTCTTC TTAGA-3Ј; cyclin D1 forward, 5Ј-TCCTGTGCTGCGA AGTGGAAAC-3Ј; cyclin D1 reverse, 5Ј-AAATCGTGCGGGGTCATTGC-3; pS2 forward, 5Ј-GAGGCCCAGACAGAGACGTG-3Ј; and pS2 reverse, 5Ј-CCCTGCAGAAGTGTCTAAAATTCA-3Ј.…”

Ectopic expression of RhoBTB2 inhibits migration and invasion of human breast cancer cells

“…As described previously, 44 cell migration was measured in a Boyden chamber using Transwell filters obtained from Corning (Cambridge, MA). Cells transfected with either RhoBTB2 expression or control vectors (1 x 10 5 ) in 0.5 mL serum-free medium were placed in the upper…”

Notch Signaling in CD66+ Cells Drives the Progression of Human Cervical Cancers

“…We investigated the role of Notch in the progression of cervical squamous cell carcinomas by examining its expression and function in the context of CD66 þ cells. CD66 expression has been earlier associated with TGFb and Src mediated invasion and metastasis of epithelial cancer cell lines (24)(25)(26)(27)(28). The expression of CD66 has been examined in primary adenocarcinomas (29) and its function has been explored using established cell lines.…”