Identifying cancer driver genes from functional genomics screens.

With the emerging advances made in genomics and functional genomics approaches, there is a critical and growing unmet need to integrate plural datasets in order to identify driver genes in cancer. An integrative approach, with the convergence of multiple types of genetic evidence, can limit false positives through a posterior filtering strategy and reduce the need for multiple hypothesis testing to identify true cancer vulnerabilities. We performed a pooled shRNA screen against 906 human genes in the oral cancer cell line AW13516 in triplicate.

Up-regulation of the kinase gene by progesterone activates the AP-1-NDRG1 axis in both PR-positive and -negative breast cancer cells.

Preoperative progesterone intervention has been shown to confer a survival benefit to breast cancer patients independently of their progesterone receptor (PR) status. This observation raises the question how progesterone affects the outcome of PR-negative cancer. Here, using microarray and RNA-Seq-based gene expression profiling and ChIP-Seq analyses of breast cancer cells, we observed that the serum- and glucocorticoid-regulated kinase gene () and the tumor metastasis-suppressor gene N-Myc downstream regulated gene 1 () are up-regulated and that the microRNAs and targeting the 3'-UTR of are down-regulated in response to progesterone.

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer.

The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n = 25) and recurrent mutations in 14% tumors (n = 44); along with co-occurring KRAS mutation in 7% tumors (n = 44). We demonstrate that ERBB2 heterodimerizes with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells.

Evaluation of genotoxic and modulatory effects of Nyctanthes arbor-tristis calyx extract and the isolated crocin in Ames' assay.

Flowers of the plant Nyctanthes arbor-tristis (NAT) are widely used in the traditional medicinal systems of several Asian countries. In the present study, potential genotoxicity and modulatory effects of ethanolic extract of NAT flower calyx (NAT FCE) and crocin, a carotenoid principle were evaluated employing standard Salmonella assay. Experiments evaluating the genotoxic potential of NAT FCE and crocin, with and without the S9-activation in TA 98, TA 100 and TA 102 showed a lack of increase in revertant mutants.

Suppression of error prone pathway is responsible for antimutagenic activity of honey.

Honey, both unifloral (Syzygiumcumini) and bifloral, demonstrated strong antimutagenicity against physical (UV, γ) and chemical (ethylmethane sulfonate) mutagens as ascertained by rpoB/RifR and Ames tests. The effect of honey was evaluated in radiation (UV or γ) exposed Escherichia coli cells for SOS response, a well known error prone repair pathway known to significantly contribute to mutagenicity by quantifying LexA repressor level, measuring cell filamentation frequency, and prophage induction by SIVET (Selectable--In-Vivo Expression Technology) assay. LexA was almost completely degraded, phenotypically long filamentous cells (∼30 μm) were formed, and SIVET induction frequency was increased in radiation exposed E.

Clastogenic and mutagenic effects of bisphenol A: an endocrine disruptor.

Bisphenol A (BPA) is a well-known endocrine disruptor (ED) which represents a major toxicological and public health concern due to its widespread exposure to humans. BPA has been reported to induce DNA adduct and aneuploidy in rodents. Recent studies in humans depicted its association with recurrent miscarriages and male infertility due to sperm DNA damage indicating that BPA might have genotoxic activity.