RGD Reference Report - Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia. - Rat Genome Database

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Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia.

Authors: Lotan, TL  Lyon, M  Huo, D  Taxy, JB  Brendler, C  Foster, BA  Stadler, W  Rinker-Schaeffer, CW 
Citation: Lotan TL, etal., J Pathol. 2007 Aug;212(4):386-94.
RGD ID: 2293334
Pubmed: PMID:17577251   (View Abstract at PubMed)
DOI: DOI:10.1002/path.2194   (Journal Full-text)

Identification of the signalling cascades that are differentially activated during prostatic tumourigenesis is a crucial step in the search for future molecular targets in this disease. The stress-activated protein kinase (SAPK) signalling cascade culminates in the phosphorylation of the JNK and p38 mitogen-activated protein kinases (MAPKs). Recently, the upstream activators of these proteins, the MAPK kinases (MKKs), have been implicated as inhibitors of tumour progression in a variety of clinical and experimental tumour models. This study evaluates MKK4, MKK6 and MKK7 expression during prostate cancer progression in humans and in the transgenic adenocarcinoma of a mouse prostate (TRAMP) model of prostate tumourigenesis. Benign prostate, prostatic intraepithelial neoplasia (PIN) lesions and tumour tissues were collected from 37 TRAMP mice. Additionally, six tissue microarrays were constructed with tumours from a matched group of 102 men who underwent radical prostatectomy. Tissues from 20 patients with extensive high-grade prostatic intraepithelial neoplasia (HGPIN) were also analysed. For all samples, immunohistochemical staining for MKK4, MKK6 and MKK7 was scored in normal and neoplastic glands. Staining intensities of MKK4, MKK6 and MKK7 were significantly increased in HGPIN and prostate cancer compared to surrounding normal glands in both the TRAMP and human samples (p < 0.0001 for all markers). Increased levels of MKK4 or MKK7 correlated with higher pathological stage at prostatectomy (p = 0.01 and p = 0.04). Using multivariate analysis, there was no association between protein levels and time to biochemical recurrence in the human samples. The up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression in both TRAMP and human tissues highlights an important role for the SAPK signalling cascade in prostatic neoplasia. The finding that higher MKK4 and MKK7 expression is associated with higher-stage prostatic tumours underscores the dynamic regulation of these proteins during prostatic tumourigenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MAP2K4Humanprostate carcinoma in situ disease_progressionIEP protein:increased expressionRGD 
MAP2K6Humanprostate carcinoma in situ disease_progressionIEP protein:increased expressionRGD 
MAP2K7Humanprostate carcinoma in situ disease_progressionIEP protein:increased expressionRGD 
Map2k4Ratprostate carcinoma in situ disease_progressionISORGD:1316000 RGD 
Map2k4Mouseprostate carcinoma in situ disease_progressionISORGD:1316000 RGD 
Map2k6Ratprostate carcinoma in situ disease_progressionISORGD:732805 RGD 
Map2k6Mouseprostate carcinoma in situ disease_progressionISORGD:732805 RGD 
Map2k7Mouseprostate carcinoma in situ disease_progressionISORGD:1347407 RGD 
Map2k7Ratprostate carcinoma in situ disease_progressionISORGD:1347407 RGD 
MAP2K4HumanProstatic Neoplasms  IEP protein:increased expression:tumor:increased in high-grade prostatic intraepithelial neoplasias and tumor tissues (p<0.0001)RGD 
MAP2K6HumanProstatic Neoplasms  IEP protein:increased expression:tumor:increased in high-grade prostatic intraepithelial neoplasias and tumor tissues (p<0.0001)RGD 
MAP2K7HumanProstatic Neoplasms  IEP protein:increased expression:tumor:increased in high-grade prostatic intraepithelial neoplasias and tumor tissues (p<0.0001)RGD 
Map2k4MouseProstatic Neoplasms  IEP protein:increased expression:tumor:increased in high-grade prostatic intraepithelial neoplasias and tumor tissues (p<0.0001)RGD 
Map2k4RatProstatic Neoplasms  ISORGD:1316000 RGD 
Map2k6RatProstatic Neoplasms  ISORGD:732805 RGD 
Map2k6MouseProstatic Neoplasms  IEP protein:increased expression:tumor:increased in high-grade prostatic intraepithelial neoplasias and tumor tissues (p<0.0001)RGD 
Map2k7MouseProstatic Neoplasms  IEP protein:increased expression:tumor:increased in high-grade prostatic intraepithelial neoplasias and tumor tissues (p<0.0001)RGD 
Map2k7RatProstatic Neoplasms  ISORGD:1347407 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map2k4  (mitogen activated protein kinase kinase 4)
Map2k6  (mitogen-activated protein kinase kinase 6)
Map2k7  (mitogen activated protein kinase kinase 7)

Genes (Mus musculus)
Map2k4  (mitogen-activated protein kinase kinase 4)
Map2k6  (mitogen-activated protein kinase kinase 6)
Map2k7  (mitogen-activated protein kinase kinase 7)

Genes (Homo sapiens)
MAP2K4  (mitogen-activated protein kinase kinase 4)
MAP2K6  (mitogen-activated protein kinase kinase 6)
MAP2K7  (mitogen-activated protein kinase kinase 7)


Additional Information