Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway
| Autor: | Nomeli P. Nunez, Amy W. Wong, Emily Schrader, Karen Poh, Qiwei X Paulson, Jina Hong, Renee E. Stubbins |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Cancer Research
Breast Neoplasms Biology Real-Time Polymerase Chain Reaction lcsh:RC254-282 Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer Stroma Cell Movement Biomarkers Tumor Cell Adhesion Tumor Cells Cultured medicine Humans metastasis Neoplasm Invasiveness RNA Messenger Cell adhesion Nm23 Cell Proliferation Oligonucleotide Array Sequence Analysis 030304 developmental biology 0303 health sciences Ethanol Cell growth alcohol Gene Expression Profiling Research Central Nervous System Depressants Integrin alphaV NM23 Nucleoside Diphosphate Kinases medicine.disease invasion lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oncology Apoptosis 030220 oncology & carcinogenesis Cancer cell Cancer research Female Signal transduction ITGA5 Signal Transduction |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 30, Iss 1, p 75 (2011) Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| DOI: | 10.1186/1756-9966-30-75 |
| Popis: | Background Alcohol consumption is an established risk factor for breast cancer metastasis. Yet, the mechanism by which alcohol promotes breast cancer metastases is unknown. The ability of cancer cells to invade through tissue barriers (such as basement membrane and interstitial stroma) is an essential step towards establishing cancer metastasis. In the present study, we identify and examine the roles of two genes, Nm23 and ITGA5, in alcohol-induced breast cancer cell invasion. Methods Human breast cancer T47D cells were treated with ethanol at various concentrations. Boyden chamber invasion assays were used to measure cellular invasive ability. The mRNA expression level of metastasis suppressor genes including Nm23 was determined by qRT-PCR. ITGA5 was identified using a qRT-PCR array of 84 genes important for cell-cell and cell-extracellular matrix interactions. Nm23 overexpression in addition to Nm23- and ITGA5 knock-down were used to determine the role of the Nm23-ITGA5 pathway on cellular invasive ability of T47D cells. Protein expression levels were verified by Western blot. Results Alcohol increased the invasive ability of human breast cancer T47D cells in a dose-dependent manner through the suppression of the Nm23 metastatic suppressor gene. In turn, Nm23 down-regulation increased expression of fibronectin receptor subunit ITGA5, which subsequently led to increased cellular invasion. Moreover, Nm23 overexpression was effective in suppressing the effects of alcohol on cell invasion. In addition, we show that the effects of alcohol on invasion were also inhibited by knock-down of ITGA5. Conclusions Our results suggest that the Nm23-ITGA5 pathway plays a critical role in alcohol-induced breast cancer cell invasion. Thus, regulation of this pathway may potentially be used to prevent the establishment of alcohol-promoted metastases in human breast cancers. |
| Databáze: | OpenAIRE |
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