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TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer.

Knight JF, Shepherd CJ, Rizzo S, Brewer D, Jhavar S, Dodson AR, Cooper CS, Eeles R, Falconer A, Kovacs G, Garrett MD, Norman AR, Shipley J, Hudson DL - Br. J. Cancer (2008)

Bottom Line: RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling.We identified 112 and 267 genes defining basal and luminal populations, respectively.Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Carcinogenesis, The Bob Champion Prostate Stem Cell Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.

ABSTRACT
Prostate cancer is the most frequently diagnosed male cancer, and its clinical outcome is difficult to predict. The disease may involve the inappropriate expression of genes that normally control the proliferation of epithelial cells in the basal layer and their differentiation into luminal cells. Our aim was to identify novel basal cell markers and assess their prognostic and functional significance in prostate cancer. RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling. We identified 112 and 267 genes defining basal and luminal populations, respectively. The transcription factor TEAD1 and the ubiquitin ligase c-Cbl were identified as novel basal cell markers. Knockdown of either marker using siRNA in prostate cell lines led to decreased cell growth in PC3 and disrupted acinar formation in a 3D culture system of RWPE1. Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics. These data are consistent with basal features impacting on the development and clinical course of prostate cancers.

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Related in: MedlinePlus

Kaplan–Meier curves. Kaplan–Meier analysis of overall and disease-specific survival for prostate cancers stained for TEAD1 (A and B) and c-Cbl (C). TEAD1 staining scored for either distribution (A) or intensity (B).
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fig3: Kaplan–Meier curves. Kaplan–Meier analysis of overall and disease-specific survival for prostate cancers stained for TEAD1 (A and B) and c-Cbl (C). TEAD1 staining scored for either distribution (A) or intensity (B).

Mentions: To determine the clinical significance of TEAD1 and c-Cbl expression in prostate tumours, TMAs were stained for the two markers. Staining and patient data for positive cores are given in Table 1,with examples of typical staining patterns in Figure 2B. As shown by immunofluorescent staining, TEAD1 was localised to basal cell nuclei, whereas that for c-Cbl was cytoplasmic. In some strongly stained regions of the TMA, c-Cbl also appeared to be perinuclear (Figure 2B C2). The scoring systems are described in the Materials and Methods. Kaplan–Meier survival curves for TEAD1 and c-Cbl, representing deaths from all causes and prostate cancer-specific deaths, are shown in Figure 3. Staining distribution (focal or diffuse) and staining intensity for TEAD1 were considered as separate parameters. Diffuse staining was found to correlate with a poorer patient prognosis than focal (P=0.0092) (Figure 3A). However, this was not a significant factor in multivariate analysis because of a strong correlation with Gleason score, with diffuse TEAD1 staining found in predominately high Gleason cancers (Table 1). Staining intensity for TEAD1 showed a clear overlap in patient survival for groups 1 and 2, and patients with the highest intensity staining (group 3) had a highly significant reduced survival rate (P=0.0009) (Figure 3B). For both parameters, these differences are most striking in the prostate cancer-specific survival data.


TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer.

Knight JF, Shepherd CJ, Rizzo S, Brewer D, Jhavar S, Dodson AR, Cooper CS, Eeles R, Falconer A, Kovacs G, Garrett MD, Norman AR, Shipley J, Hudson DL - Br. J. Cancer (2008)

Kaplan–Meier curves. Kaplan–Meier analysis of overall and disease-specific survival for prostate cancers stained for TEAD1 (A and B) and c-Cbl (C). TEAD1 staining scored for either distribution (A) or intensity (B).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600693&req=5

fig3: Kaplan–Meier curves. Kaplan–Meier analysis of overall and disease-specific survival for prostate cancers stained for TEAD1 (A and B) and c-Cbl (C). TEAD1 staining scored for either distribution (A) or intensity (B).
Mentions: To determine the clinical significance of TEAD1 and c-Cbl expression in prostate tumours, TMAs were stained for the two markers. Staining and patient data for positive cores are given in Table 1,with examples of typical staining patterns in Figure 2B. As shown by immunofluorescent staining, TEAD1 was localised to basal cell nuclei, whereas that for c-Cbl was cytoplasmic. In some strongly stained regions of the TMA, c-Cbl also appeared to be perinuclear (Figure 2B C2). The scoring systems are described in the Materials and Methods. Kaplan–Meier survival curves for TEAD1 and c-Cbl, representing deaths from all causes and prostate cancer-specific deaths, are shown in Figure 3. Staining distribution (focal or diffuse) and staining intensity for TEAD1 were considered as separate parameters. Diffuse staining was found to correlate with a poorer patient prognosis than focal (P=0.0092) (Figure 3A). However, this was not a significant factor in multivariate analysis because of a strong correlation with Gleason score, with diffuse TEAD1 staining found in predominately high Gleason cancers (Table 1). Staining intensity for TEAD1 showed a clear overlap in patient survival for groups 1 and 2, and patients with the highest intensity staining (group 3) had a highly significant reduced survival rate (P=0.0009) (Figure 3B). For both parameters, these differences are most striking in the prostate cancer-specific survival data.

Bottom Line: RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling.We identified 112 and 267 genes defining basal and luminal populations, respectively.Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Carcinogenesis, The Bob Champion Prostate Stem Cell Team, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.

ABSTRACT
Prostate cancer is the most frequently diagnosed male cancer, and its clinical outcome is difficult to predict. The disease may involve the inappropriate expression of genes that normally control the proliferation of epithelial cells in the basal layer and their differentiation into luminal cells. Our aim was to identify novel basal cell markers and assess their prognostic and functional significance in prostate cancer. RNA from basal and luminal cells isolated from benign tissue by immunoguided laser-capture microdissection was subjected to expression profiling. We identified 112 and 267 genes defining basal and luminal populations, respectively. The transcription factor TEAD1 and the ubiquitin ligase c-Cbl were identified as novel basal cell markers. Knockdown of either marker using siRNA in prostate cell lines led to decreased cell growth in PC3 and disrupted acinar formation in a 3D culture system of RWPE1. Analyses of prostate cancer tissue microarray staining established that increased protein levels of either marker were associated with decreased patient survival independent of other clinicopathological metrics. These data are consistent with basal features impacting on the development and clinical course of prostate cancers.

Show MeSH
Related in: MedlinePlus