Name: Transcription profiling by array of human breast cancer cell line SKBR3 retinoic acid receptor alpha, targetted with all-trans retinoic acid, lapatnib and lapatnib and all-trans retinoic acid combined to investigate a novel miRNA expression profile
Keywords: transcription profiling by array

Dataset Information

Transcription profiling by array of human breast cancer cell line SKBR3 retinoic acid receptor alpha, targetted with all-trans retinoic acid, lapatnib and lapatnib and all-trans retinoic acid combined to investigate a novel miRNA expression profile

ABSTRACT: In SKBR3 cells, simultaneous targeting of RARë± with all-trans retinoic acid (ATRA) and HER2 with lapatinib results in synergistic anti-tumor responses. SKBR3 cells were treated with vehicle (DMSO), lapatinib (100 nM), ATRA (100 nM) or lapatinib+ATRA for 36 hours and miRNA expression profile was determined by one-color Agilent microarray experiments.

ORGANISM(S): Homo sapiens

SUBMITTER: Maddalena Fratelli

PROVIDER: E-MTAB-3097 | ArrayExpress | 2015-04-30

REPOSITORIES: ArrayExpress

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Publications

MicroRNA networks regulated by all-trans retinoic acid and Lapatinib control the growth, survival and motility of breast cancer cells.

Fisher James Neil JN Fisher James Neil JN Terao Mineko M Fratelli Maddalena M Kurosaki Mami M Paroni Gabriela G Zanetti Adriana A Gianni Maurizio M Bolis Marco M Lupi Monica M Tsykin Anna A Goodall Gregory J GJ Garattini Enrico E

Oncotarget 20150501 15

SKBR3-cells, characterized by ERBB2/RARA co-amplification, represent a subgroup of HER2+ breast-cancers sensitive to all-trans retinoic acid (ATRA) and Lapatinib. In this model, the two agents alone or in combination modulate the expression of 174 microRNAs (miRs). These miRs and predicted target-transcripts are organized in four interconnected modules (Module-1 to -4). Module-1 and Module-3 consist of ATRA/Lapatinib up-regulated and potentially anti-oncogenic miRs, while Module-2 contains ATRA/ ...[more]

PMID: 25961594

Similar Datasets

Project description:Forty-two cell lines recapitulating mammary carcinoma heterogeneity were profiled for all-trans retinoic acid (ATRA) sensitivity. Luminal and ER(+) (estrogen-receptor-positive) cell lines are generally sensitive to ATRA, while refractoriness/low sensitivity is associated with a Basal phenotype and HER2 positivity. Indeed, only 2 Basal cell lines (MDA-MB157 and HCC-1599) are highly sensitive to the retinoid. Sensitivity of HCC-1599 cells is confirmed in xenotransplanted mice. Short-term tissue-slice cultures of surgical samples validate the cell-line results and support the concept that a high proportion of Luminal/ER(+) carcinomas are ATRA sensitive, while triple-negative (Basal) and HER2-positive tumors tend to be retinoid resistant. Pathway-oriented analysis of the constitutive gene-expression profiles in the cell lines identifies RAR? as the member of the retinoid pathway directly associated with a Luminal phenotype, estrogen positivity and ATRA sensitivity. RAR?3 is the major transcript in ATRA-sensitive cells and tumors. Studies in selected cell lines with agonists/antagonists confirm that RAR? is the principal mediator of ATRA responsiveness. RAR? over-expression sensitizes retinoid-resistant MDA-MB453 cells to ATRA anti-proliferative action. Conversely, silencing of RAR? in retinoid-sensitive SKBR3 cells abrogates ATRA responsiveness. All this is paralleled by similar effects on ATRA-dependent inhibition of cell motility, indicating that RAR? may mediate also ATRA anti-metastatic effects. We define gene sets of predictive potential which are associated with ATRA sensitivity in breast cancer cell lines and validate them in short-term tissue cultures of Luminal/ER(+) and triple-negative tumors. In these last models, we determine the perturbations in the transcriptomic profiles afforded by ATRA. The study provides fundamental information for the development of retinoid-based therapeutic strategies aimed at the stratified treatment of breast cancer subtypes.

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