PMID- 20198306 OWN - NLM STAT- MEDLINE DCOM- 20100519 LR - 20100303 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 25 IP - 4 DP - 2010 Apr TI - Expression of MLN64 influences cellular matrix adhesion of breast cancer cells, the role for focal adhesion kinase. PG - 573-80 AB - The metastatic lymph node 64 (MLN64) gene was initially identified as highly expressed in the metastatic lymph node from breast cancer. It is localized in q12-q21 of the human chromosome 17 and is often co-amplified with erbB-2. However, the role played by MLN64 in breast cancer remains unclear. In the present study, the expression of MLN64 was examined in a breast cancer cohort using quantitative real-time PCR and immunohistochemical staining. It demonstrated that MLN64 was highly expressed in breast tumours compared to corresponding background tissues at both transcript level and protein level. The elevated level of MLN64 transcripts was correlated with the poor prognosis and overall survival of the patients. A panel of breast cancer cell sublines was subsequently developed by knockdown of MLN64 expression. Loss of MLN64 expression in MCF-7 cells resulted in a significant reduction of cell growth (absorbance for MCF-7DeltaMLN64 being 0.87+/-0.07, P<0.01 vs. wild-type control (MCF-7WT 1.13+/-0.06) and transfection control (MCF-7pEF 1.27+/-0.05). In cell-matrix adhesion assay, MDA-MB-231DeltaMLN64 cells showed a significant increase in adhesion (86+/-14), p<0.01 compared with both MDA-MB-231WT (61+/-20) and MDA-MB-231pEF (45+/-27). Further investigations demonstrated an increase in protein level of the focal adhesion kinase (FAK) in MDA-MB-231DeltaMLN64 cells using Western blot analysis and immunofluorescent staining of FAK. Moreover, addition of FAK inhibitor to these cells diminished the effect of MLN64 on cell-matrix adhesion, suggesting that FAK contributed to the increased adhesion in MDA-MB-231DeltaMLN64 cells. In conclusion, MLN64 is overexpressed in breast cancer, and its level correlates with poor prognosis and patient survival. MLN64 contributes to the development and progression of breast cancer through the regulation of cell proliferation and adhesive capacity. FAU - Cai, Wei AU - Cai W AD - Metastasis and Angiogenesis Research Group, Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. FAU - Ye, Lin AU - Ye L FAU - Sun, Jiabang AU - Sun J FAU - Mansel, Robert E AU - Mansel RE FAU - Jiang, Wen G AU - Jiang WG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Carrier Proteins) RN - 0 (Membrane Proteins) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (STARD3 protein, human) RN - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases) SB - IM MH - Breast Neoplasms/*enzymology/genetics/*pathology MH - Carrier Proteins/genetics/*metabolism MH - Cell Adhesion/drug effects MH - Cell Line, Tumor MH - Extracellular Matrix/drug effects/*metabolism MH - Female MH - Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors/*metabolism MH - Gene Expression Regulation, Neoplastic/drug effects MH - Gene Knockdown Techniques MH - Humans MH - Membrane Proteins/genetics/*metabolism MH - Protein Kinase Inhibitors/pharmacology MH - RNA, Messenger/genetics/metabolism MH - Survival Analysis MH - Treatment Outcome EDAT- 2010/03/04 06:00 MHDA- 2010/05/21 06:00 CRDT- 2010/03/04 06:00 PHST- 2010/03/04 06:00 [entrez] PHST- 2010/03/04 06:00 [pubmed] PHST- 2010/05/21 06:00 [medline] PST - ppublish SO - Int J Mol Med. 2010 Apr;25(4):573-80.