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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 specifically alters the expression of EMT components and re-programmes chromatin transcription towards a more metastatic profile. (A) p23-V5 tagged ectopic expression was induced in LNCaP-p23 cells as explained before prior to cells being harvested and 10 μg of total lysate resolved by SDS-PAGE, transferred onto nitrocellulose membranes and probed with specific antibodies against vinculin, V5 and α-tubulin. Signal was quantified using ImageJ and normalised against the corresponding loading control. Results are the mean of 3 independent experiments. (B) LNCaP_p23 cells were incubated with or without DOX for 10 days prior to being harvested for RNA extraction. 500 ng of RNA were reverse-transcribed and qRT-PCR performed using specific primers against LAMB1, KYNU, CTSD and PMP22 genes. GAPDH was used as the reference gene. Results are the mean ± 1 STDEV of three independent experiments performed in triplicate. *p value ≤0.05 and **p value ≤0.005 (Student's t test).
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fig8: p23 specifically alters the expression of EMT components and re-programmes chromatin transcription towards a more metastatic profile. (A) p23-V5 tagged ectopic expression was induced in LNCaP-p23 cells as explained before prior to cells being harvested and 10 μg of total lysate resolved by SDS-PAGE, transferred onto nitrocellulose membranes and probed with specific antibodies against vinculin, V5 and α-tubulin. Signal was quantified using ImageJ and normalised against the corresponding loading control. Results are the mean of 3 independent experiments. (B) LNCaP_p23 cells were incubated with or without DOX for 10 days prior to being harvested for RNA extraction. 500 ng of RNA were reverse-transcribed and qRT-PCR performed using specific primers against LAMB1, KYNU, CTSD and PMP22 genes. GAPDH was used as the reference gene. Results are the mean ± 1 STDEV of three independent experiments performed in triplicate. *p value ≤0.05 and **p value ≤0.005 (Student's t test).

Mentions: To unravel the mechanism by which p23 affects cell motility, the protein expression levels of a panel of epithelial-to-mesenchymal transition (EMT) markers (snail, E-cadherin, vimentin, β–catenin) was analysed in the inducible LNCaP-p23 line. No changes in any of the markers analysed were observed despite increased V5-p23 expression, suggesting p23 does not exert its effects upon cell motility in this manner (Figure 8A). However vinculin, a component of focal adhesions, was significantly increased (1.4 fold) in cells ectopically expressing p23, supporting previous observations that knocking down p23 reduces vinculin levels (Echtenkamp et al., 2011) and suggesting p23 may alter cell motility via modulating the interaction between the plasma membrane and the actin cytoskeleton.


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 specifically alters the expression of EMT components and re-programmes chromatin transcription towards a more metastatic profile. (A) p23-V5 tagged ectopic expression was induced in LNCaP-p23 cells as explained before prior to cells being harvested and 10 μg of total lysate resolved by SDS-PAGE, transferred onto nitrocellulose membranes and probed with specific antibodies against vinculin, V5 and α-tubulin. Signal was quantified using ImageJ and normalised against the corresponding loading control. Results are the mean of 3 independent experiments. (B) LNCaP_p23 cells were incubated with or without DOX for 10 days prior to being harvested for RNA extraction. 500 ng of RNA were reverse-transcribed and qRT-PCR performed using specific primers against LAMB1, KYNU, CTSD and PMP22 genes. GAPDH was used as the reference gene. Results are the mean ± 1 STDEV of three independent experiments performed in triplicate. *p value ≤0.05 and **p value ≤0.005 (Student's t test).
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fig8: p23 specifically alters the expression of EMT components and re-programmes chromatin transcription towards a more metastatic profile. (A) p23-V5 tagged ectopic expression was induced in LNCaP-p23 cells as explained before prior to cells being harvested and 10 μg of total lysate resolved by SDS-PAGE, transferred onto nitrocellulose membranes and probed with specific antibodies against vinculin, V5 and α-tubulin. Signal was quantified using ImageJ and normalised against the corresponding loading control. Results are the mean of 3 independent experiments. (B) LNCaP_p23 cells were incubated with or without DOX for 10 days prior to being harvested for RNA extraction. 500 ng of RNA were reverse-transcribed and qRT-PCR performed using specific primers against LAMB1, KYNU, CTSD and PMP22 genes. GAPDH was used as the reference gene. Results are the mean ± 1 STDEV of three independent experiments performed in triplicate. *p value ≤0.05 and **p value ≤0.005 (Student's t test).
Mentions: To unravel the mechanism by which p23 affects cell motility, the protein expression levels of a panel of epithelial-to-mesenchymal transition (EMT) markers (snail, E-cadherin, vimentin, β–catenin) was analysed in the inducible LNCaP-p23 line. No changes in any of the markers analysed were observed despite increased V5-p23 expression, suggesting p23 does not exert its effects upon cell motility in this manner (Figure 8A). However vinculin, a component of focal adhesions, was significantly increased (1.4 fold) in cells ectopically expressing p23, supporting previous observations that knocking down p23 reduces vinculin levels (Echtenkamp et al., 2011) and suggesting p23 may alter cell motility via modulating the interaction between the plasma membrane and the actin cytoskeleton.

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