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GSE82307
Homo sapiens
65 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To elucidate the mechanisms underlying relapse from chemotherapy in multiple myeloma we performed a longitudinal study of 33 patients entered into Total Therapy protocols investigating them using gene expression profiling, high resolution copy number arrays and whole exome sequencing. The study illustrates the mechanistic importance of acquired mutations in known myeloma driver genes and the critical nature of bi-allelic inactivation events affecting tumor suppressor genes, especially TP53. The end result being resistance to apoptosis and increased proliferation rates, which drive relapse by Darwinian type clonal evolution. The number of copy number aberration changes and bi-allelic inactivation of tumor suppressor genes was increased in GEP70 high risk, consistent with genomic instability being a key feature of high risk. In conclusion, the study highlights the impact of acquired genetic events, which enhance the evolutionary fitness level of myeloma propagating cells to survive multi-agent chemotherapy and to result in relapse.
Publication Title
Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In order to properly understand whether xenoestrogens act as estrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. Because the estrogen-dependent gene expression is one of the primary biomarkers of estrogenic action, we have assessed effects of three doses of exogenous estradiol (0.1, 1.0 and 10 g/kg of body weight/day) on the mammary gland morphology and gene expression profiles by microarray analysis of prepubertal male and female rats of both sexes compared to untreated controls. Estradiol was administered subcutaneously with minipumps from weaning at PND21 to the end of the experiment at PND33. The data suggest that the male mammary is a sensitive tissue for estrogenicity assessment.
Publication Title
Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol.
Sample Metadata Fields
Sex
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The linkage between nutrition and cancer prevention is an intriguing concept that is gaining widespread support based on epidemiological and animal studies. Multiple mechanisms likely underlie dietary protection against cancer, with effects influenced by target tissue response, cell-cell interactions and developmental context. Given the negative correlation between breast cancer incidence and intake of soy foods by Asian women, and the increasing consumption of soy protein-based formula by infants in the Western world, we have studied soy protein isolate (SPI) used in most infant formula as a paradigm to evaluate diet as a risk factor in a rodent model of mammary cancer. We previously demonstrated that lifetime exposure to dietary SPI reduced the incidence of N-methyl-N-nitrosourea-induced mammary tumors in young adult rats relative to those fed the control diet Casein (CAS). This protection was associated with increased tumor suppressor PTEN and decreased Wnt signaling component expression in mammary epithelial cells at postnatal day (PND) 50 prior to carcinogen insult. To identify early events contributing to mammary tumor suppression by diet, we used Affymetrix RAE230A GeneChips containing 14280 probe sets and the GeneSpring Robust Multi-array program to analyze genomic profiles of mammary glands of prepubertal (PND21) rats lifetime exposed to SPI or CAS.
Publication Title
Early soy exposure via maternal diet regulates rat mammary epithelial differentiation by paracrine signaling from stromal adipocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The role of diet in the prevention of breast cancer is widely accepted, yet little is known on how early dietary effects mitigate adult cancer risk. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (GEN). We previously showed lower chemically-induced mammary tumor incidence in young adult rats with lifetime dietary intake of soy protein isolate (SPI), a highly refined soy product in infant formula, than in those fed the control diet Casein (CAS). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed CAS, SPI, or supplemental GEN-based diets. We identified mammary epithelial genes regulated by SPI (79 total) and GEN (99 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally cluster in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or GEN using QPCR. Wnt pathway inhibition by GEN was supported by lower Cyclin D1 immunoreactivity in mammary ductal epithelium of GEN relative to CAS and SPI, despite their comparable levels of membrane-localized E-cadherin and -catenin. Identification of distinct GEN and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer.
Publication Title
Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A Krppel-like factor 9 (Klf9) regulated network in HEC-1-A endometrial carcinoma cells encompassing adhesion proteins, steroid- and menstrual cycle-regulated proteins of the uterine endometrium, novel membrane proteins, and nuclear receptors
Publication Title
The Krüppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression.
Sample Metadata Fields
No sample metadata fields
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