Transcriptomics

Dataset Information

0

Receptor-independent ectopic activity of PROLACTIN predicts aggressive lung tumors and indicates HDACi-based therapeutic strategies.


ABSTRACT: Aim: PROLACTIN (PRL), normally produced by the pituitary gland, acts through its receptor (PRL-R) to initiate a signalling cascade to the genome. PRL can also be produced by cancer cells and become oncogenic by stimulating its receptor following an autocrine or paracrine route. Here we investigated the oncogenic activities of PRL in lung cancer. Results: PRL is ectopically activated in a subset of very aggressive lung tumours, associated with a rapid fatal outcome, in our cohort of 293 lung tumour patients as well as in an external independent series of patients. An investigation of the molecular basis of PRL adverse effects surprisingly showed an absence of PRL-R expression in the vast majority of PRL-expressing lung tumours. Additionally, a detailed analysis of the ectopically expressed PRL transcripts in lung tumours and cell lines revealed systematic alterations of its first exons encoding the signal peptide. Finally, the transcriptomes of two PRL expressing lung cancer cell lines, with or without silencing of PRL, showed that PRL directly or indirectly sustains the expression of a group of genes that are frequently up-regulated in a variety of unrelated cancers. Interestingly, the gene signature repressed by PRL ectopic expression in lung tumour cells is also specifically up-regulated by HDAC inhibitor treatment or HDAC1/2/3 knock-down. Innovation and conclusion: Altogether, this work sheds lights on the poorly understood impact of the recently-shown large-scale out-of-context gene activity in cancer and also suggests that PRL-expressing aggressive lung cancers could be particularly responsive to a HDAC inhibitor-based treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE49544 | GEO | 2014/08/05

SECONDARY ACCESSION(S): PRJNA214224

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2014-08-05 | E-GEOD-49544 | biostudies-arrayexpress
2011-03-16 | E-GEOD-22812 | biostudies-arrayexpress
2011-03-16 | GSE22812 | GEO
2019-07-25 | GSE130513 | GEO
2020-03-25 | GSE115413 | GEO
2022-03-23 | PXD012098 | Pride
2014-04-14 | E-GEOD-28685 | biostudies-arrayexpress
2023-06-02 | GSE230054 | GEO
2019-05-16 | E-MTAB-7727 | biostudies-arrayexpress
2014-04-14 | GSE28685 | GEO