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Transcription profiling of human breast tumors and their paired normal tissues

ABSTRACT: Microarray is widely used to monitor gene expression changes in breast cancer. The transcriptomic changes in breast cancer is commonly occured during the transition of normal cells to cancerous cells. This is the first study on gene expression profiling of multi ethnic of Malaysian breast cancer patients (Malays, Chinese and Indian). We aim to identify differentially expressed genes between tumors and normal tissues. We have identified a set of 33 significant differentially expressed genes in the tumor vs. normal group at p<0.001. We study the gene expression patterns of 43 breast tumors and their paired normal control by using Affymetrix genechip U133A. We have identified a set of 33 significant differentially expressed genes in the tumor vs. normal group at p<0.001. Experiment Overall Design: Total RNAs were extracted from breast cancer and normal tissues. Samples were processed and hybridized on the chip for 16 hours. At the end of the study, we obtained a total of 86 set of gene expression data, which were from 43 tumors and 43 normal tissues. The gene expression were then compared between the tumor and normal groups.

ORGANISM(S): Homo sapiens

SUBMITTER: Bong Ivyna PN

PROVIDER: S-ECPF-GEOD-15852 | biostudies-other |

REPOSITORIES: biostudies-other

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Project description:Tumorigenic breast cancer cells characterized by CD44 expression and low or undetectable CD24 levels (CD44+/CD24-/low) may be resistant to chemotherapy and therefore responsible for cancer relapse. Paired breast cancer core biopsies before and after neoadjuvant chemotherapy or lapatinib were obtained and as single cell suspensions stained using antibodies against CD24, CD44, and lineage markers, and then analyzed by flow cytometry. Mammosphere (MS) formation in culture was compared before and after treatment. Global gene expression differences between cancer cells bearing CD44+/CD24-/low cells and all other sorted cells, and between cancer MS and the primary bulk invasive cancers were analyzed. We report that CD44+/CD24-/low tumorigenic breast cancer cells were intrinsically chemoresistant - chemotherapy led to increased CD44+/CD24-/low cells, increased self-renewal capacity on MS assays, and enhanced tumorigeneicity in immunocompromised SCID/Beige mice. Conversely, in patients with HER2 overexpressing tumors, the EGFR/HER2 tyrosine kinase inhibitor, lapatinib decreased CD44+/CD24-/low cells, with the majority of these patients after conventional therapy achieving pathologic complete response, a validated surrogate marker for long-term survival. Gene transcription pathways that underlie chemoresistant, MS-forming CD44+/CD24-/low cells involve genes belonging to stem cell self-renewal, Wnt signaling, and early development pathways. Experiment Overall Design: Cells from human breast tumors were grown as mammospheres (MS). Experiment Overall Design: Isolated single cell suspensions from primary breast cancers were plated onto non-adherent (polyhema-coated) plastic, counted with a hematocytometer, and 20,000 cells were then seeded into a 6-well ultra-low attachment plate supplemented with 2mL MEGM, with the addition of 2 mL of freshly unfrozen MEGM every 3-4 days. Gene expression profiles were taken of both MS and primary bulk tumors and compared with each other.

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Transcription profiling of human breast tumors and their paired normal tissues

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