Limits...
The co-chaperone p23 promotes prostate cancer motility and metastasis.

Cano LQ, Lavery DN, Sin S, Spanjaard E, Brooke GN, Tilman JD, Abroaf A, Gaughan L, Robson CN, Heer R, Mauri F, de Rooij J, Driouch K, Bevan CL - Mol Oncol (2014)

Bottom Line: Moreover, p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti-androgens.This was in contrast to the HSP90 inhibitor 17-AAG, which did not modulate expression of the cochaperone - important given the HSP90-independent roles we and others have previously described for p23.We propose that increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression, and that p23 is a plausible secondary target in combination with HSP90 inhibition as a potential therapy for advanced prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: Androgen Signalling Laboratory, Imperial Centre for Translational & Experimental Medicine, Imperial College London, London W12 0NN, UK.

No MeSH data available.


Related in: MedlinePlus

p23 expression directly correlates with patient survival and disease progression. Immunohistochemistry was performed on human prostate cancer tissue microarrays and cores scored for intensity of nuclear and cytoplasmic p23 staining. (A) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients (n = 53). Low = score 0 or 1, High = score 2 or 3. (B) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients with confirmed metastatic disease (n = 31). (C) Correlation between the intensity of nuclear and cytoplasmic p23 expression with the development of metastatic lesions in prostate cancer patients with Gleason score ≤7. *p value ≤0.05 (one-tailed Student's t test).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4510206&req=5

fig7: p23 expression directly correlates with patient survival and disease progression. Immunohistochemistry was performed on human prostate cancer tissue microarrays and cores scored for intensity of nuclear and cytoplasmic p23 staining. (A) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients (n = 53). Low = score 0 or 1, High = score 2 or 3. (B) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients with confirmed metastatic disease (n = 31). (C) Correlation between the intensity of nuclear and cytoplasmic p23 expression with the development of metastatic lesions in prostate cancer patients with Gleason score ≤7. *p value ≤0.05 (one-tailed Student's t test).

Mentions: As prostate cancer cells expressing higher p23 appeared to have increased invasive potential in our assays, we hypothesized that patients expressing high levels of p23 protein may be more prone to developing metastatic lesions and consequently have shorter survival times. To investigate this, immunohistochemistry was performed on prostate cancer tissue microarrays and specimens scored for primary Gleason grade and for nuclear and cytoplasmic p23 staining on a scale of 0–3 (3 = highest intensity). An inverse correlation between nuclear p23 expression and patient survival was observed. Patients with high nuclear p23 expression showed significantly shorter overall survival, with mean survival decreasing from 67 to 40.2 months and median from 57.4 to 31.7 months (Figure 7A and Table 1, p value = 0.017). Disease-specific survival was also decreased in patients with high nuclear p23, with mean survival decreasing from 90.2 to 52.3 months (Supplemental Figure 2A and Supplemental Table S2). The survival differences were more significant in patients with lower grade tumours (Gleason grade ≤7, data not shown). Even in patients with confirmed metastatic lesions, there was a significant difference in survival between patients with high and low p23 (Figure 7B); reduction in survival was significantly correlated with high p23 nuclear expression suggesting p23 could serve as a poor prognostic indicator.


The co-chaperone p23 promotes prostate cancer motility and metastasis.

Cano LQ, Lavery DN, Sin S, Spanjaard E, Brooke GN, Tilman JD, Abroaf A, Gaughan L, Robson CN, Heer R, Mauri F, de Rooij J, Driouch K, Bevan CL - Mol Oncol (2014)

p23 expression directly correlates with patient survival and disease progression. Immunohistochemistry was performed on human prostate cancer tissue microarrays and cores scored for intensity of nuclear and cytoplasmic p23 staining. (A) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients (n = 53). Low = score 0 or 1, High = score 2 or 3. (B) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients with confirmed metastatic disease (n = 31). (C) Correlation between the intensity of nuclear and cytoplasmic p23 expression with the development of metastatic lesions in prostate cancer patients with Gleason score ≤7. *p value ≤0.05 (one-tailed Student's t test).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4510206&req=5

fig7: p23 expression directly correlates with patient survival and disease progression. Immunohistochemistry was performed on human prostate cancer tissue microarrays and cores scored for intensity of nuclear and cytoplasmic p23 staining. (A) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients (n = 53). Low = score 0 or 1, High = score 2 or 3. (B) Kaplan Meier graph depicting relation between overall survival and p23 nuclear staining in prostate cancer patients with confirmed metastatic disease (n = 31). (C) Correlation between the intensity of nuclear and cytoplasmic p23 expression with the development of metastatic lesions in prostate cancer patients with Gleason score ≤7. *p value ≤0.05 (one-tailed Student's t test).
Mentions: As prostate cancer cells expressing higher p23 appeared to have increased invasive potential in our assays, we hypothesized that patients expressing high levels of p23 protein may be more prone to developing metastatic lesions and consequently have shorter survival times. To investigate this, immunohistochemistry was performed on prostate cancer tissue microarrays and specimens scored for primary Gleason grade and for nuclear and cytoplasmic p23 staining on a scale of 0–3 (3 = highest intensity). An inverse correlation between nuclear p23 expression and patient survival was observed. Patients with high nuclear p23 expression showed significantly shorter overall survival, with mean survival decreasing from 67 to 40.2 months and median from 57.4 to 31.7 months (Figure 7A and Table 1, p value = 0.017). Disease-specific survival was also decreased in patients with high nuclear p23, with mean survival decreasing from 90.2 to 52.3 months (Supplemental Figure 2A and Supplemental Table S2). The survival differences were more significant in patients with lower grade tumours (Gleason grade ≤7, data not shown). Even in patients with confirmed metastatic lesions, there was a significant difference in survival between patients with high and low p23 (Figure 7B); reduction in survival was significantly correlated with high p23 nuclear expression suggesting p23 could serve as a poor prognostic indicator.

Bottom Line: Moreover, p23 protein levels significantly increased upon treatment with not only androgen but also clinically relevant anti-androgens.This was in contrast to the HSP90 inhibitor 17-AAG, which did not modulate expression of the cochaperone - important given the HSP90-independent roles we and others have previously described for p23.We propose that increased p23 expression may allow cells to acquire a more aggressive phenotype, contributing to disease progression, and that p23 is a plausible secondary target in combination with HSP90 inhibition as a potential therapy for advanced prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: Androgen Signalling Laboratory, Imperial Centre for Translational & Experimental Medicine, Imperial College London, London W12 0NN, UK.

No MeSH data available.


Related in: MedlinePlus