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Expression of NF-κB-related proteins and their modulation during TNF-α-provoked apoptosis in prostate cancer cells.
Prostate. 2012 Jan; 72(1):40-50.P

Abstract

BACKGROUND

The involvement of TNF-α in cancer development is controversial, since this cytokine was reported to act either as tumor promoter or suppressor. TNF-α may activate signaling pathways critical for life/death decisions, such as mitogen-activated protein kinases (MAPKs) and the anti-apoptotic NF-κB pathway. In this work, we investigate the activation status of NF-κB-related proteins in human prostate cancerous versus normal epithelium, and the alterations in the NF-κB pathway in relation to cell death in TNF-α-treated LNCaP (androgen-independent cells) and PC3 (androgen-independent) prostate cancer cell lines.

METHODS

The expression of phospho-p38-MAPK, phospho-IKK-α/β and phospho-IκB-α, total IκB-α, and p65- and p50-NF-κB, were analyzed by immunohistochemistry in cancerous and normal prostate samples. The toxicity of TNF-α in LNCaP and PC3 cells, with or without kinase and NF-κB inhibitors, was assessed by changes on viability (MTT assay) and apoptosis (loss of DNA, annexin-V binding, and caspase cleavage/activation). Expression of NF-κB-related proteins in these cell lines was measured by Western blot.

RESULTS

Phospho-IκB-α, phospho-IKK-α/β and phospho-p38 levels, cytoplasmic p50 to IκB-α ratio, and nuclear p50 and p65, levels, were increased in cancerous epithelium, suggesting activation of the NF-κB pathway in prostatic malignance. TNF-α caused apoptosis with higher efficacy in LNCaP cells, and this response was potentiated by p38-MAPK inhibitor (LNCaP cells) and IKK-β inhibitor (both cell lines). However, the protective action of IKK-β was mediated by NF-κB only in LNCaP cells.

CONCLUSIONS

IKK-β mediates both NF-κB-dependent and -independent anti-apoptotic functions in prostate cancerous epithelium. IKK-β and p38-MAPK may represent useful therapeutic targets against prostate cancer.

Authors+Show Affiliations

Departamento de Biología Celular y Genética, Universidad de Alcalá, Madrid, Spain. gonzalo.rodriguezb@uah.esNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21520161

Citation

Rodríguez-Berriguete, Gonzalo, et al. "Expression of NF-κB-related Proteins and Their Modulation During TNF-α-provoked Apoptosis in Prostate Cancer Cells." The Prostate, vol. 72, no. 1, 2012, pp. 40-50.
Rodríguez-Berriguete G, Fraile B, Paniagua R, et al. Expression of NF-κB-related proteins and their modulation during TNF-α-provoked apoptosis in prostate cancer cells. Prostate. 2012;72(1):40-50.
Rodríguez-Berriguete, G., Fraile, B., Paniagua, R., Aller, P., & Royuela, M. (2012). Expression of NF-κB-related proteins and their modulation during TNF-α-provoked apoptosis in prostate cancer cells. The Prostate, 72(1), 40-50. https://doi.org/10.1002/pros.21404
Rodríguez-Berriguete G, et al. Expression of NF-κB-related Proteins and Their Modulation During TNF-α-provoked Apoptosis in Prostate Cancer Cells. Prostate. 2012;72(1):40-50. PubMed PMID: 21520161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of NF-κB-related proteins and their modulation during TNF-α-provoked apoptosis in prostate cancer cells. AU - Rodríguez-Berriguete,Gonzalo, AU - Fraile,Benito, AU - Paniagua,Ricardo, AU - Aller,Patricio, AU - Royuela,Mar, Y1 - 2011/04/25/ PY - 2011/02/23/received PY - 2011/03/25/accepted PY - 2011/4/27/entrez PY - 2011/4/27/pubmed PY - 2012/1/19/medline SP - 40 EP - 50 JF - The Prostate JO - Prostate VL - 72 IS - 1 N2 - BACKGROUND: The involvement of TNF-α in cancer development is controversial, since this cytokine was reported to act either as tumor promoter or suppressor. TNF-α may activate signaling pathways critical for life/death decisions, such as mitogen-activated protein kinases (MAPKs) and the anti-apoptotic NF-κB pathway. In this work, we investigate the activation status of NF-κB-related proteins in human prostate cancerous versus normal epithelium, and the alterations in the NF-κB pathway in relation to cell death in TNF-α-treated LNCaP (androgen-independent cells) and PC3 (androgen-independent) prostate cancer cell lines. METHODS: The expression of phospho-p38-MAPK, phospho-IKK-α/β and phospho-IκB-α, total IκB-α, and p65- and p50-NF-κB, were analyzed by immunohistochemistry in cancerous and normal prostate samples. The toxicity of TNF-α in LNCaP and PC3 cells, with or without kinase and NF-κB inhibitors, was assessed by changes on viability (MTT assay) and apoptosis (loss of DNA, annexin-V binding, and caspase cleavage/activation). Expression of NF-κB-related proteins in these cell lines was measured by Western blot. RESULTS: Phospho-IκB-α, phospho-IKK-α/β and phospho-p38 levels, cytoplasmic p50 to IκB-α ratio, and nuclear p50 and p65, levels, were increased in cancerous epithelium, suggesting activation of the NF-κB pathway in prostatic malignance. TNF-α caused apoptosis with higher efficacy in LNCaP cells, and this response was potentiated by p38-MAPK inhibitor (LNCaP cells) and IKK-β inhibitor (both cell lines). However, the protective action of IKK-β was mediated by NF-κB only in LNCaP cells. CONCLUSIONS: IKK-β mediates both NF-κB-dependent and -independent anti-apoptotic functions in prostate cancerous epithelium. IKK-β and p38-MAPK may represent useful therapeutic targets against prostate cancer. SN - 1097-0045 UR - https://www.unboundmedicine.com/medline/citation/21520161/Expression_of_NF_��B_related_proteins_and_their_modulation_during_TNF_��_provoked_apoptosis_in_prostate_cancer_cells_ DB - PRIME DP - Unbound Medicine ER -