Aberrant expression of E-cadherin and beta-catenin in human prostate cancer☆

Jaggi, Meena; Johansson, Sonny L.; Baker, John J.; Smith, Lynette M.; Galich, Anton; Balaji, K.C.

doi:10.1016/j.urolonc.2005.03.024

Cited by 86 publications

(93 citation statements)

References 22 publications

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“…Importantly, these results support the use of HDAC inhibitors and PPAR␥ agonists in the treatment of prostate cancer. Finally, consistent with previous results (19,29), we showed that E-cadherin expression is lost in most of prostate adenocarcinoma samples (Fig. 8C), suggesting that the association of PPAR␥ agonists and HDAC inhibitors might be of interest to reinduce E-cadherin expression and subsequently inhibit invasion.…”

Section: Synergistic Action Of Ppar␥ Agonists and Hdac Inhibitorssupporting

confidence: 92%

Peroxisome Proliferator-Activated Receptor γ Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer

Annicotte

Iankova

Miard

et al. 2006

Molecular and Cellular Biology

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Peroxisome proliferator-activated receptor ␥ (PPAR␥) might not be permissive to ligand activation in prostate cancer cells. Association of PPAR␥ with repressing factors or posttranslational modifications in PPAR␥ protein could explain the lack of effect of PPAR␥ ligands in a recent randomized clinical trial. Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPAR␥ agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy. We show that the combination treatment impairs the bone-invasive potential of prostate cancer cells in mice. In addition, we demonstrate that expression of E-cadherin, a protein involved in the control of cell migration and invasion, is highly up-regulated in the presence of valproic acid and pioglitazone. We show that E-cadherin expression responds only to the combination treatment and not to single PPAR␥ agonists, defining a new class of PPAR␥ target genes. These results open up new therapeutic perspectives in the treatment of prostate cancer.Prostate cancer is the most common form of cancer in men and the second leading cause of cancer deaths. Tumor growth is originally androgen dependent. Androgens exert their effects through activation of the androgen receptor (AR), a member of the hormone nuclear receptor superfamily. In the mature prostatic gland, the AR regulates the expression of genes involved in cell division and proliferation of the epithelial cells (26). The AR is also involved in several other aspects of prostate cellular metabolism, including lipid biosynthesis, and controls the production of specialized secretory proteins with prostate-restricted expression, such as prostate-specific antigen (PSA) (26). When prostate cancer is still hormone dependent, androgen ablation therapy causes regression of the tumor (18), likely through inactivation of the transcription of the AR target genes. However, the durability of this response is inadequate and many men develop recurrent androgen-independent prostate cancer, which has a very poor prognosis (see reference 11 for a review). Other nuclear receptors or locally produced factors that interact with nuclear receptors are likely involved in cell proliferation, differentiation, and apoptosis in the prostate. The peroxisome proliferator-activated receptor ␥ (PPAR␥) is one such factor. PPAR␥ is another member of the hormone nuclear receptor superfamily. As for most of the other members of this family, its activity is regulated by ligands. Prostaglandin J2 and the antidiabetic drugs thiazolidinediones have been determined to be natural and synthetic ligands of PPAR␥, respectively (for a review, see reference 9). PPAR␥ is highly expressed in the adipose tissue and is required for its development through regulation of the expression of adipocyte-specific genes, such as lipoprotein lipase or the fatty acid transport protein aP2. PPAR␥ is expressed in several other tissues in add...

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Section: Synergistic Action Of Ppar␥ Agonists and Hdac Inhibitorssupporting

confidence: 92%

Peroxisome Proliferator-Activated Receptor γ Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer

Annicotte

Iankova

Miard

et al. 2006

Molecular and Cellular Biology

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“…The expression of E-cadherin is inversely correlated to tumor grade, even within one RP specimen containing both benign and malignant tissues (Jaggi et al 2005). This also underlines the diYculty of E-cadherin expression analysis using prostate biopsies compared to PC specimens.…”

Section: E-cadherinmentioning

confidence: 75%

“…This indicates that the loss of adherens junctions is an event occurring early in tumor development, assuming PIN lesions as precursors of prostate carcinoma. (Jaggi et al 2005) However, the loss of membranous -catenin occurs at a very low rate and does not correlate with tumor stage or grade. The loss of membranous -catenin could be a direct consequence of loss of adherens junctions early in tumor development.…”

Section: N-cadherinmentioning

confidence: 99%

New experimental markers for early detection of high-risk prostate cancer: role of cell–cell adhesion and cell migration

Mól

Geldof

Meijer

et al. 2007

J Cancer Res Clin Oncol

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Today's treatment and diagnosis of prostate cancer still exhibit major limitations. The search for new and additional prognostic markers is therefore still an actual Weld of interest. Potential markers involved in numerous biological processes in the tumor cell have been investigated intensively. For therapeutic interventions it is important to distinguish between harmless and aggressive disease in an early stage. Therefore the subject of this review is limited to markers associated with those functional processes, which discriminate early stage aggressive, metastatic cancer from harmless disease. Important processes in this respect are: altered cell adhesion and cellular migration. E-cadherin, N-cadherin, -catenin, integrins, focal adhesion kinase, connexins and matrix metalloproteinases all appear promising biological markers associated with the early stage metastatic process in prostate cancer. Here we discuss their potential to become valid biological markers based on literature data. Thus far, none of these markers proved to be a valid individual marker by itself due to prostate cancer heterogeneity and transient expression. Analyzing a combination of the potential markers discussed in this review is expected to be a better approach toward discriminating high-from low-risk tumors in an early stage of prostate cancer.

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“…Expression of E-cadherin is typically reduced in prostate cancer. [14][15][16][17][18][19] Some studies have found an association between E-cadherin expression and prostate cancer grade or stage, while others have failed to do so; however, loss of E-cadherin and the onset of expression of N-cadherin are observed in high-grade prostate cancer. 17,[20][21][22] We previously found strong expression of cadherin-10 mRNA in human prostate.…”

mentioning

confidence: 99%

The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer

et al. 2008

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During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In nonneoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14-and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.

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Aberrant expression of E-cadherin and beta-catenin in human prostate cancer☆

Cited by 86 publications

References 22 publications

Peroxisome Proliferator-Activated Receptor γ Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer

Peroxisome Proliferator-Activated Receptor γ Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer

New experimental markers for early detection of high-risk prostate cancer: role of cell–cell adhesion and cell migration

The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer

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