原创力文档validation of the cancer biochip system as a 3d sirna screening tool for breast cancer targets癌症生物芯片的验证系统作为一个3 d sirna乳腺癌的筛查工具的目标.pdfVIP
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validation of the cancer biochip system as a 3d sirna screening tool for breast cancer targets癌症生物芯片的验证系统作为一个3 d sirna乳腺癌的筛查工具的目标
Validation of the Cancer BioChip System as a 3D siRNA
Screening Tool for Breast Cancer Targets
Joie N. Marhefka, Rula A. Abbud-Antaki*
Falcon Genomics, Inc., Pittsburgh, Pennsylvania, United States of America
Abstract
Genomic studies have revealed that breast cancer consists of a complex biological process with patient-specific genetic
variations, revealing the need for individualized cancer diagnostic testing and selection of patient-specific optimal therapies.
One of the bottlenecks in translation of genomic breakthroughs to the clinic is the lack of functional genomic assays that
have high clinical translatability. Anchorage-independent three-dimensional (3D) growth assays are considered to be the
gold-standard for chemosensitivity testing, and leads identified with these assays have high probability of clinical success.
The Cancer BioChip System (CBCS) allows for the simultaneous, quantitative, and real time evaluation of multitudes of
anchorage-independent breast cancer cell growth inhibitors. We employed a Test Cancer BioChip that contains silencing
RNAs (siRNAs) targeting cancer-related genes to identify 3D-specific effectors of breast cancer cell growth. We compared
the effect of these siRNAs on colony growth of the hormone receptor positive (MCF7) and Human Epidermal Growth Factor
Receptor 2/c- Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2/c-erb-b2) positive (SK-BR-3) cells on the Test
Cancer BioChip. Our results confirmed cell-specific inhibition of MCF7 and SK-BR-3 colony formation by estrogen receptor a
(ESR1) and (ERBB2) siRNA, respectively. Both cell lines were also suppressed by Phosphoinositide-3-kinase Catalytic, alpha
Polypeptide (PIK3CA) siRNA. Interestingly, we have observed responses to siRNA that are unique to this 3D setting. For
example, ß-actin (ACTB) siRNA suppressed colony growth
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