Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from human adrenocortical H295R cells expressing a doxycyclin-inducible shRNA targeting CTNNB1

ABSTRACT: We used the H295R cell line, human adrenocortical cells, harboring a heterozygous CTNNB1 (beta-catenin) gene mutation affecting the GSK3 beta-phosphorylation site (S45P) and leading to constitutive transcriptional activity of beta-catenin-LEF/TCF. Whole-transcript gene expression was analyzed in three stable clones of H295R cells expressing a doxycycline-inducible shRNA targeting CTNNB1 mRNA and in a control clone, without or with doxycycline for 5 days.

ORGANISM(S): Homo sapiens

SUBMITTER: Bruno Ragazzon

PROVIDER: E-MTAB-3330 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma.

Lefèvre L L Omeiri H H Drougat L L Hantel C C Giraud M M Val P P Rodriguez S S Perlemoine K K Blugeon C C Beuschlein F F de Reyniès A A Rizk-Rabin M M Bertherat J J Ragazzon B B

Oncogenesis 20150727

Adrenocortical cancer (ACC) is a very aggressive tumor, and genomics studies demonstrate that the most frequent alterations of driver genes in these cancers activate the Wnt/β-catenin signaling pathway. However, the adrenal-specific targets of oncogenic β-catenin-mediating tumorigenesis have not being established. A combined transcriptomic analysis from two series of human tumors and the human ACC cell line H295R harboring a spontaneous β-catenin activating mutation was done to identify the Wnt/ ...[more]

PMID: 26214578

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Project description:Stable activation of the WNT signaling effector beta-catenin (CTNNB1(ex3) in ovarian granulosa cells results in the formation of premalignant lesions that develop into granulosa cell tumors (GCTs) spontaneously later in life. Loss of the tumor suppressor gene Pten accelerates GCT formation in the CTNNB1 strain. Conversely, expression of oncogenic KRASG12D causes the dramatic arrest of proliferation, differentiation and apoptosis in granulosa cells, and consequently, small abnormal follicle-like structures devoid of oocytes accumulate in the ovary. Because of the potent anti-proliferative effects of KRASG12D in granulosa cells, we sought to determine if KRASG12D would block precancerous lesion and tumor formation in follicles of the CTNNB1 mutant mice. Unexpectedly, transgenic Ctnnb1;Kras mutant mice developed early-onset GCTs leading to premature death in a manner similar to theCtnnb1;Pten mutant mice. Moreover, the GCTs in the Ctnnb1;Kras mutant mice exhibited increased GC proliferation, decreased apoptosis and impaired differentiation. Microarray and RT-PCR analyses revealed that ovaries from mice expressing dominant-stable CTNNB1 with either Pten loss or KRAS activation were unpredictably similar. Specifically, gene regulatory processes induced by CTNNB1 were mostly enhanced by either KRAS activation or Pten loss in remarkably similar patterns and degree. Furthermore, the concomitant activation of CTNNB1 and KRAS in Sertoli cells resulted in the development of granulosa cell tumors of the testis. RT-PCR studies showed a partial overlap in gene regulatory processes associated with tumor development in the ovary and testis. Together, these results suggest that KRAS activation and Pten loss induce GCT development from premalignant lesions via highly similar molecular mechanisms. four samples: average of two wild type samples (previously submitted as GSM403220 and GSM403221), beta-Catenin constitutively active mutant, beta-Catenin;Pten double mutant, and beta-Catenin;Kras(G12D) double mutant

Dataset Information

Expression data from human adrenocortical H295R cells expressing a doxycyclin-inducible shRNA targeting CTNNB1

Publications

Combined transcriptome studies identify AFF3 as a mediator of the oncogenic effects of β-catenin in adrenocortical carcinoma.

Similar Datasets

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