PPARγ expression in breast cancer: clinical value and correlation with ERβ

Papadaki, Ioanna; Mylona, Eleni; Giannopoulou, Ioanna; Markaki, S.; Keramopoulos, Antonios; Nakopoulou, Lydia

doi:10.1111/j.1365-2559.2005.02056.x

Cited by 59 publications

(53 citation statements)

References 28 publications

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“…The importance of high STS and CYP1B1 expression in the estrogen metabolism/ER-h factor prompts the hypothesis that increased availability of estrogen and its conversion to genotoxic metabolites may contribute to the development of this tumor subset. High PPAR-g receptor levels also contributed to this factor, consistent with data indicating that PPAR-g expression is correlated with ER-h levels and might modulate estrogen actions (21).…”

Section: Discussionsupporting

confidence: 87%

Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study

et al. 2007

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The objective of this study was to evaluate the coexpression patterns of hormonal markers in breast cancer tissue and their relationship with pathologic characteristics and epidemiologic risk factors. We evaluated the expression of 17 markers by immunohistochemistry in 842 invasive breast carcinomas collected in a population-based case-control study conducted in Poland. Based on marker correlations, factor analysis identified four major coexpression patterns ( factors): ''nuclear receptor factor'' [estrogen receptor (ER)-A, progesterone receptor, androgen receptor, cyclin D1, and aromatase], ''estrogen metabolism/ER-B factor'' (ER-B, peroxisome proliferator-activated receptor-;, steroid sulfatase, estrogen sulfonotransferase, and cytochrome P450 1B1), ''HER2 factor'' (human epidermal growth factor receptor 2, E-cadherin, cyclooxygenase-2, aromatase, steroid sulfatase), and ''proliferation factor'' (cytokeratin 5, cytokeratin 5/6, epidermal growth factor receptor, P53). Three of these factors corresponded to molecular subtypes previously defined by expression profiling; however, the estrogen metabolism/ER-B factor seemed to be distinctive. High scores for this factor were associated with high tumor grade (P heterogeneity = 0.02), younger age at menarche (P heterogeneity = 0.04), lower current body mass index among premenopausal women (P heterogeneity = 0.01), and older age at menopause (P heterogeneity = 0.04). High scores for the proliferation factor were also associated with early menarche (P heterogeneity < 0.0001), and in contrast to the estrogen metabolism/ ER-B factor, higher current body mass index among premenopausal women (P heterogeneity = 0.03). Our analysis of hormonal pathway markers independently confirmed several previously defined molecular subtypes identified by gene expression profiling and augmented these findings by suggesting the existence of additional relationships related to ER-B and enzymes involved in hormone metabolism. [Cancer Res 2007;67(21):10608-17]

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Section: Discussionsupporting

confidence: 87%

Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study

et al. 2007

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“…However, no apparent phenotype was observed in the mammary tissues of mice lacking Ppar␥ expression in mammary epithelium (11), indicating that Ppar␥-dependent effects may be subtle or that another factor can compensate in its absence. One unanswered question is whether loss of Pparg expression enhances or suppresses oncogene-induced breast carcinogenesis in vivo (52). A potential clue was obtained recently from the observation that in a large prospective study of patients with diabetes mellitus receiving the glucose-lowering PPAR␥ agonist pioglitazone (Actos) for at least 2.5 years, a significant reduction (P ϭ 0.034) in the incidence of breast cancer was observed only in the group receiving pioglitazone (n ϭ 3/2,605) compared with the blinded placebo control group (n ϭ 11/ 2,633) (http://www.proactive-results.com/).…”

Section: Discussionmentioning

confidence: 99%

Parvin-β Inhibits Breast Cancer Tumorigenicity and Promotes CDK9-Mediated Peroxisome Proliferator-Activated Receptor Gamma 1 Phosphorylation

Johnstone

Mongroo

Rich

et al. 2008

Molecular and Cellular Biology

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The integrin-linked kinase (ILK) is a multifunctional adaptor protein and serine/threonine kinase that binds the cytoplasmic domains of ␤1-and ␤3-integrin receptor subunits (18,19,68). ILK is a key constituent of the molecular bridge between cell surface integrins and the cortical actin cytoskeleton, namely, focal adhesion complexes (32,49,57). In addition to a structural role, integrin-extracellular matrix (ECM) engagement or stimulation with growth factors activates ILK kinase activity in a phosphatidylinositol 3Ј kinase-dependent manner, resulting in phosphorylation of downstream substrates, such as AKT Ser473 and glycogen synthase kinase 3␤ Ser9 (13). ILK also provides integrins with a connection to certain receptor tyrosine kinases via the adaptor proteins PINCH1/2 and NCK2 (64, 72). Overexpression of ILK in cell lines results in anchorage-independent growth, E-cadherin loss, increased invasiveness, and tumorigenicity in nude mice (13,19). Moreover, increased ILK expression and activity in mouse mammary tumor virus ILK transgenic mice leads to mammary hyperplasias and breast cancers (67). These data suggest that ILK activity must be regulated carefully for effective tumor suppression in vivo and raise the possibility that modulators of ILK function or kinase activity could be deregulated during epithelial oncogenesis.Parvin-␣, -␤, and -␥ comprise a small family of widely expressed ILK-binding proteins with tandem calponin homology domains (30,48,51,57,70). The two best-characterized members, Parvin-␣ and -␤, interact directly with the ILK kinase domain in a mutually exclusive manner (73) and modulate both its kinase activity and connections to the actin cytoskeleton (51), although the molecular mechanisms underlying these actions are only now beginning to emerge (43,66,73). Less is known about Parvin-␥ function.Data from several studies suggest that Parvin-␣ and Parvin-␤ may have divergent actions in the regulation of ILK signaling and cytoskeletal dynamics. For example, Parvin-␣ was reported to facilitate ILK-mediated phosphorylation of AKT Ser473, with subsequent protection from apoptosis (13, 73), whereas Parvin-␤ overexpression in HeLa cells promoted apoptosis (73). Parvin-␤ also inhibited ILK kinase activity and reduced AKT Ser473 and glucogen synthase kinase 3␤ Ser9 phosphorylation in response to epidermal growth factor stimulation, as previously reported by us (43), consistent with negative regulation of ILK signaling. In contrast to Parvin-␣, Parvin-␤ directly bound to the actin-binding protein ␣-actinin and was required for proper focal adhesion formation, lamellipodium maturation, and cell spreading (69, 70). In addition to its reg-* Corresponding author. Mailing address:

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“…Jiang et al (43) found lower mRNA levels in breast cancer patients with high-risk tumors. Papadaki et al (44) investigated breast cancer tissues immunohistochemically and found low rates of PPARg to be prognostic of shorter disease-free survival times. It is of interest to note, however, that although they used the same antibody we used in our study, they reported a predominantly cytoplasmic and even membranous immunostaining, which they subjected to statistical evaluation.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ Is Highly Expressed in Pancreatic Cancer and Is Associated With Shorter Overall Survival Times

Kristiansen

Jacob

Buckendahl

et al. 2006

Clinical Cancer Research

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Purpose: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that has been implicated in carcinogenesis and progression of various solid tumors, including pancreatic carcinoma. We aimed to clarify the expression patterns of PPARγ in pancreatic ductal carcinomas and to correlate these to clinicopathologic variables, including patient survival. Experimental Design: Array-based expression profiling of 19 microdissected carcinomas and 14 normal ductal epithelia was conducted. Additionally, Western blots of pancreatic cancer cell lines and paraffinized tissue of 129 pancreatic carcinomas were immunostained for PPARγ. For statistical analysis, Fisher's exact test, χ2 test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied. Results: Expression profiles showed a strong overexpression of PPARγ mRNA (change fold, 6.9; P = 0.04). Immunohistochemically, PPARγ expression was seen in 71.3% of pancreatic cancer cases. PPARγ expression correlated positively to higher pT stages and higher tumor grade. Survival analysis showed a significant prognostic value for PPARγ, which was found to be independent in the clinically important subgroup of node-negative tumors. Conclusions: PPARγ is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPARγ in tumor progression of pancreatic cancer.

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PPARγ expression in breast cancer: clinical value and correlation with ERβ

Abstract: These results indicate the favourable impact of PPARgamma expression on disease-free survival of patients with ductal breast carcinoma and its possible cooperation with ERbeta in exerting that favourable effect.

Cited by 59 publications

References 28 publications

Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study

Hormonal Markers in Breast Cancer: Coexpression, Relationship with Pathologic Characteristics, and Risk Factor Associations in a Population-Based Study

Parvin-β Inhibits Breast Cancer Tumorigenicity and Promotes CDK9-Mediated Peroxisome Proliferator-Activated Receptor Gamma 1 Phosphorylation

Peroxisome Proliferator-Activated Receptor γ Is Highly Expressed in Pancreatic Cancer and Is Associated With Shorter Overall Survival Times

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