The early effects of rapid androgen deprivation on human prostate cancer
The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa).Therefore, understanding how ARs regulate the human transcriptome is of paramountimportance. The early effects of castration on human PCa have not previously beenstudied 27 patients medically castrated with degarelix 7...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2015
|
| _version_ | 1826264372957151232 |
|---|---|
| author | Shaw, G Whitaker, H Corcoran, M Dunning, M Luxton, H Kay, J Massie, C Miller, J Lamb, A Ross-Adams, H Russell, R Nelson, A Eldridge, M Lynch, A Ramos-Montoya, A Mills, I Taylor, A Arlt, W Shah, N Warren, A Neal, D |
| author_facet | Shaw, G Whitaker, H Corcoran, M Dunning, M Luxton, H Kay, J Massie, C Miller, J Lamb, A Ross-Adams, H Russell, R Nelson, A Eldridge, M Lynch, A Ramos-Montoya, A Mills, I Taylor, A Arlt, W Shah, N Warren, A Neal, D |
| author_sort | Shaw, G |
| collection | OXFORD |
| description | The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa).Therefore, understanding how ARs regulate the human transcriptome is of paramountimportance. The early effects of castration on human PCa have not previously beenstudied 27 patients medically castrated with degarelix 7 d before radical prostatec-tomy. We used mass spectrometry, immunohistochemistry, and gene expression array(validated by reverse transcription-polymerase chain reaction) to compare resectedtumour with matched, controlled, untreated PCa tissue. All patients had levels ofserum androgen, with reduced levels of intraprostatic androgen at prostatectomy.We observed differential expression of known androgen-regulated genes (TMPRSS2,KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upre-gulated following castration. AR regulation ofa-methylacyl-CoA racemase expressionand three other genes (FAM129A, RAB27A,andKIAA0101) was confirmed. Upregulationof oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia andwas associated with differential expression of ESR1-regulated genes and correlatedwith proliferation (Ki-67 expression).Patient summary:This first-in-man study defines the rapid gene expression changestaking place in prostate cancer (PCa) following castration. Expression levels of the genesthat the androgen receptor regulates are predictive of treatment outcome. Upregulationof oestrogen receptor 1 is a mechanism by which PCa cells may survive despitecastration |
| first_indexed | 2024-03-06T20:06:45Z |
| format | Journal article |
| id | oxford-uuid:292663eb-2b33-47d6-83a7-0f91cbc4bb87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:06:45Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:292663eb-2b33-47d6-83a7-0f91cbc4bb872022-03-26T12:17:24ZThe early effects of rapid androgen deprivation on human prostate cancerJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:292663eb-2b33-47d6-83a7-0f91cbc4bb87EnglishSymplectic Elements at OxfordElsevier2015Shaw, GWhitaker, HCorcoran, MDunning, MLuxton, HKay, JMassie, CMiller, JLamb, ARoss-Adams, HRussell, RNelson, AEldridge, MLynch, ARamos-Montoya, AMills, ITaylor, AArlt, WShah, NWarren, ANeal, DThe androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa).Therefore, understanding how ARs regulate the human transcriptome is of paramountimportance. The early effects of castration on human PCa have not previously beenstudied 27 patients medically castrated with degarelix 7 d before radical prostatec-tomy. We used mass spectrometry, immunohistochemistry, and gene expression array(validated by reverse transcription-polymerase chain reaction) to compare resectedtumour with matched, controlled, untreated PCa tissue. All patients had levels ofserum androgen, with reduced levels of intraprostatic androgen at prostatectomy.We observed differential expression of known androgen-regulated genes (TMPRSS2,KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upre-gulated following castration. AR regulation ofa-methylacyl-CoA racemase expressionand three other genes (FAM129A, RAB27A,andKIAA0101) was confirmed. Upregulationof oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia andwas associated with differential expression of ESR1-regulated genes and correlatedwith proliferation (Ki-67 expression).Patient summary:This first-in-man study defines the rapid gene expression changestaking place in prostate cancer (PCa) following castration. Expression levels of the genesthat the androgen receptor regulates are predictive of treatment outcome. Upregulationof oestrogen receptor 1 is a mechanism by which PCa cells may survive despitecastration |
| spellingShingle | Shaw, G Whitaker, H Corcoran, M Dunning, M Luxton, H Kay, J Massie, C Miller, J Lamb, A Ross-Adams, H Russell, R Nelson, A Eldridge, M Lynch, A Ramos-Montoya, A Mills, I Taylor, A Arlt, W Shah, N Warren, A Neal, D The early effects of rapid androgen deprivation on human prostate cancer |
| title | The early effects of rapid androgen deprivation on human prostate cancer |
| title_full | The early effects of rapid androgen deprivation on human prostate cancer |
| title_fullStr | The early effects of rapid androgen deprivation on human prostate cancer |
| title_full_unstemmed | The early effects of rapid androgen deprivation on human prostate cancer |
| title_short | The early effects of rapid androgen deprivation on human prostate cancer |
| title_sort | early effects of rapid androgen deprivation on human prostate cancer |
| work_keys_str_mv | AT shawg theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT whitakerh theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT corcoranm theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT dunningm theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT luxtonh theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT kayj theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT massiec theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT millerj theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT lamba theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT rossadamsh theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT russellr theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT nelsona theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT eldridgem theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT lyncha theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT ramosmontoyaa theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT millsi theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT taylora theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT arltw theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT shahn theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT warrena theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT neald theearlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT shawg earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT whitakerh earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT corcoranm earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT dunningm earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT luxtonh earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT kayj earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT massiec earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT millerj earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT lamba earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT rossadamsh earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT russellr earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT nelsona earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT eldridgem earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT lyncha earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT ramosmontoyaa earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT millsi earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT taylora earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT arltw earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT shahn earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT warrena earlyeffectsofrapidandrogendeprivationonhumanprostatecancer AT neald earlyeffectsofrapidandrogendeprivationonhumanprostatecancer |