The PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cells

2.50
Hdl Handle:
http://hdl.handle.net/11287/593959
Title:
The PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cells
Authors:
Munkley, J.; Livermore, K. E.; McClurg, U. L.; Kalna, G.; Knight, Bridget; McCullagh, Paul; McGrath, John S; Crundwell, Malcolm; Leung, H. Y.; Robson, C. N.; Harries, L. W.; Rajan, P.; Elliott, D. J.
Abstract:
Androgen receptor (AR) signalling and the PI3K pathway mediate survival signals in prostate cancer, and have been shown to regulate each other by reciprocal negative feedback, such that inhibition of one activates the other. Understanding the reciprocal regulation of these pathways is important for disease management as tumour cells can adapt and survive when either single pathway is inhibited pharmacologically. We recently carried out genome-wide exon-specific profiling of prostate cancer cells to identify novel androgen-regulated transcriptional events. Here we interrogated this dataset for novel androgen-regulated genes associated with the PI3K pathway. We find that the PI3K regulatory subunits PIK3R1 (p85alpha) and PIK3R3 (p55gamma) are direct targets of the AR which are rapidly repressed by androgens in LNCaP cells. Further characterisation revealed that the PIK3CA p110alpha catalytic subunit is also indirectly regulated by androgens at the protein level. We show that PIK3R1 mRNA is significantly under-expressed in prostate cancer (PCa) tissue, and provide data to suggest a context-dependent regulatory mechanism whereby repression of the p85alpha protein by the AR results in destabilisation of the PI3K p110alpha catalytic subunit and downstream PI3K pathway inhibition that functionally affects the properties of prostate cancer cells.
Citation:
Oncoscience. 2015;2(9):755-64.
Publisher:
Oncoscience
Journal:
Oncoscience
Issue Date:
14-Sep-2015
URI:
http://hdl.handle.net/11287/593959
PubMed ID:
26501081
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26501081/
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article
Language:
eng
ISSN:
2331-4737
Appears in Collections:
2015 RD&E publications; HeSRU publications; Exeter Clinical Laboratory International (Blood Sciences, Genetics, Cellular Pathology & Microbiology); Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorMunkley, J.en
dc.contributor.authorLivermore, K. E.en
dc.contributor.authorMcClurg, U. L.en
dc.contributor.authorKalna, G.en
dc.contributor.authorKnight, Bridgeten
dc.contributor.authorMcCullagh, Paulen
dc.contributor.authorMcGrath, John Sen
dc.contributor.authorCrundwell, Malcolmen
dc.contributor.authorLeung, H. Y.en
dc.contributor.authorRobson, C. N.en
dc.contributor.authorHarries, L. W.en
dc.contributor.authorRajan, P.en
dc.contributor.authorElliott, D. J.en
dc.date.accessioned2016-01-19T12:37:59Zen
dc.date.available2016-01-19T12:37:59Zen
dc.date.issued2015-09-14en
dc.identifier.citationOncoscience. 2015;2(9):755-64.en
dc.identifier.issn2331-4737en
dc.identifier.pmid26501081en
dc.identifier.urihttp://hdl.handle.net/11287/593959en
dc.description.abstractAndrogen receptor (AR) signalling and the PI3K pathway mediate survival signals in prostate cancer, and have been shown to regulate each other by reciprocal negative feedback, such that inhibition of one activates the other. Understanding the reciprocal regulation of these pathways is important for disease management as tumour cells can adapt and survive when either single pathway is inhibited pharmacologically. We recently carried out genome-wide exon-specific profiling of prostate cancer cells to identify novel androgen-regulated transcriptional events. Here we interrogated this dataset for novel androgen-regulated genes associated with the PI3K pathway. We find that the PI3K regulatory subunits PIK3R1 (p85alpha) and PIK3R3 (p55gamma) are direct targets of the AR which are rapidly repressed by androgens in LNCaP cells. Further characterisation revealed that the PIK3CA p110alpha catalytic subunit is also indirectly regulated by androgens at the protein level. We show that PIK3R1 mRNA is significantly under-expressed in prostate cancer (PCa) tissue, and provide data to suggest a context-dependent regulatory mechanism whereby repression of the p85alpha protein by the AR results in destabilisation of the PI3K p110alpha catalytic subunit and downstream PI3K pathway inhibition that functionally affects the properties of prostate cancer cells.en
dc.language.isoengen
dc.publisherOncoscienceen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26501081/en
dc.titleThe PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cellsen
dc.typeJournal Articleen
dc.identifier.journalOncoscienceen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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