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