Is PTEN loss associated with clinical outcome measures in human prostate cancer?

Inactivating PTEN mutations are commonly found in prostate cancer, resulting in an increased activation of Akt. In this study, we investigate the role of PTEN deletion and protein expression in the development of hormone-refractory prostate cancer using matched hormone-sensitive and hormone-refractory tumours. Fluorescent in situ hybridisation and immunohistochemistry was carried out to investigate PTEN gene deletion and PTEN protein expression in the transition from hormone-sensitive to hormone-refractory prostate cancer utilising 68 matched hormone sensitive and hormone-refractory tumour pairs (one before and one after hormone relapse). Heterogeneous PTEN gene deletion was observed in 23% of hormone sensitive tumours. This increased significantly to 52% in hormone-refractory tumours (P=0.044). PTEN protein expression was observed in the membrane, cytoplasm and the nucleus. In hormone sensitive tumours, low levels of cytoplasmic PTEN was independently associated with shorter time to relapse compared to high levels of PTEN (P=0.028, hazard ratio 0.51 (95%CI 0.27–0.93). Loss of PTEN expression in the nucleus of hormone sensitive tumours was independently associated with disease-specific survival (P=0.031, hazard ratio 0.52, 95%CI 0.29–0.95). The results from this study demonstrate a role for both cytoplasmic and nuclear PTEN in progression of prostate cancer to the hormone-refractory state.

• Publication year

  2008

• Venue

  British Journal of Cancer

• Publication date

  2008-10-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/sj.bjc.6604680PMID 18854827PMCID 2570524
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients

  2008influential reference
• The PTEN gene in locally progressive prostate cancer is preferentially inactivated by bi‐allelic gene deletion

  2006influential reference
• Observer variation in immunohistochemical analysis of protein expression, time for a change?

  2006influential reference
• The ERK1/2 pathway modulates nuclear PTEN-mediated cell cycle arrest by cyclin D1 transcriptional regulation.

  2006cited by this paper
• Class reunion: PTEN joins the nuclear crew

  2005cited by this paper
• Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import mediated by major vault protein.

  2005cited by this paper
• Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis.

  2005cited by this paper
• Akt-regulated pathways in prostate cancer

  2005cited by this paper
• Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer

  2003cited by this paper
• Current status of the molecular genetics of human prostatic adenocarcinomas

  2003cited by this paper
• PTEN: One Gene, Many Syndromes

  2003cited by this paper
• The embedded tumour: host physiology is important for the evaluation of tumour growth

  2003cited by this paper
• Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault.

  2002cited by this paper
• Oncogenes and tumor suppressor genes in prostate cancer.

  2001cited by this paper
• Role of PI3K signaling in survival and progression of LNCaP prostate cancer cells to the androgen refractory state.

  2001influential reference
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  2000cited by this paper
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  2000cited by this paper
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  2000cited by this paper
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  1999cited by this paper
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  1999cited by this paper
• Analysis of PTEN and the 10q23 region in primary prostate carcinomas

  1998cited by this paper
• Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression.

  1998cited by this paper
• Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN.

  1998cited by this paper
• Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues.

  1998cited by this paper
• The lipid phosphatase activity of PTEN is critical for its tumor supressor function.

  1998cited by this paper
• Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate adenocarcinomas.

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• Apoptosis regulating genes in prostate cancer (review).

  1998cited by this paper
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  1997cited by this paper
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  1994cited by this paper
• Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma.

  1990cited by this paper
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  1986cited by this paper

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