Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: Identification of novel molecular biomarkers for early diagnosis and therapy

Bignotti, Eliana; Tassi, Renata; Calza, Stefano; Ravaggi, Antonella; Romani, Chiara; Rossi, Elisa; Falchetti, Marcella; Odicino, Franco; Pecorelli, Sërgio; Santin, Alessandro D.

doi:10.1016/j.ygyno.2006.03.056

Cited by 94 publications

(94 citation statements)

References 35 publications

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“…Several studies have confirmed the overexpression of claudin-3 and claudin-4 in ovarian cancer [7][8][9][10][11][12][13][14], but the roles of these proteins in tumorigenesis or the mechanisms regulating them are unclear. As a first step in elucidating the role of claudin phosphorylation in ovarian cancer, we have recently shown that claudin-3 can be phosphorylated by PKA at Thr192, and that phosphorylation of this residue could lead to the disruption of TJs in ovarian cancer cells [38].…”

Section: Discussionmentioning

confidence: 99%

“…However, paradoxically, claudins have also been shown to be elevated in several cancers [5]. For example, we and others have shown that claudin-3 and claudin-4 are highly increased in ovarian cancer [7][8][9][10][11][12][13][14]. These claudins have also been shown to be elevated in prostate, pancreatic, uterine, and breast cancer [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cells

D’Souza

Indig

Morin

2007

Experimental Cell Research

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Claudin proteins belong to a large family of transmembrane proteins essential to the formation and maintenance of tight junctions (TJs). In ovarian cancer, TJ protein claudin-4 is frequently overexpressed and may have roles in survival and invasion, but the molecular mechanisms underlying its regulation are poorly understood. In this report, we show that claudin-4 can be phosphorylated by protein kinase C (PKC) at Thr189 and Ser194 in ovarian cancer cells and overexpression of a claudin-4 mutant protein mimicking the phosphorylated state results in the disruption of the barrier function. Furthermore, upon phorbol ester-mediated PKC activation of OVCA433 cells, TJ strength is decreased and claudin-4 localization is altered. Analyses using PKC inhibitors and siRNA suggest that PKCε, an isoform typically expressed in ovarian cancer cells, may be important in the TPAmediated claudin-4 phosphorylation and weakening of the TJs. Furthermore, immunofluorescence studies showed that claudin-4 and PKCε are co-localized at the TJs in these cells. The modulation of claudin-4 activity by PKCε may not only provide a mechanism for disrupting TJ function in ovarian cancer, but may also be important in the regulation of TJ function in normal epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cells

D’Souza

Indig

Morin

2007

Experimental Cell Research

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“…Tumour and normal tissues sharp-dissection, liquid nitrogen freezing, and epithelial purity checking were performed as previously reported (Bignotti et al, 2006).…”

Section: Patients and Samplesmentioning

confidence: 99%

“…Total RNA extraction, quantification, and quality assessment were performed as previously described (Bignotti et al, 2006). Labelling of samples and hybridisation to the Affymetrix Human HG-U133 Plus 2.0 oligonucleotide microarray chips (Santa Clara, CA, USA), covering over 47 000 human transcripts and variants, were performed following the manufacturer's protocols.…”

Section: Total Rna Extraction and Genechip Hybridisationmentioning

confidence: 99%

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Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas

et al. 2008

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This study identifies the genetic fingerprint of poorly differentiated endometrioid endometrial carcinomas (G3-EEC) and analyses the potential utility of trefoil factor 3 (TFF3) as novel serum marker in G3-EEC. Affymetrix microarrays were used to identify the gene expression patterns of 19 snap-frozen G3-EEC and 15 normal endometrium (NE) biopsies. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to validate TFF3 expression. Finally, TFF3 serum levels were determined by ELISA in 25 G3-EEC patients, 42 healthy controls, and in 13 endometrial hyperplasia patients. Hierarchical cluster analysis showed TFF3 as the top differentially expressed gene between 363 upregulated genes in G3-EEC, when compared with NE. Trefoil factor 3 gene expression levels analysed by qRT-PCR significantly correlated with Affymetrix results (Po0.001; rs ¼ 0.85). By immunohistochemistry, TFF3 protein was significatively more expressed in EEC compared with NE (Po0.01), with cytoplasmatic positivity in 79% G3-EEC and 18% NE. Patients harbouring G3-EECs had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients (Po0.001) or patients harbouring endometrial hyperplasia (P ¼ 0.012). In conclusion, TFF3 is highly expressed at gene and protein level in G3-EEC. Further investigations on a wider set of samples are warranted to validate TFF3 as a novel serum marker for early detection and/or monitoring of G3-EEC patients.

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Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer

Bellone

Anfossi

O’Brien

et al. 2008

Cancer

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Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: Identification of novel molecular biomarkers for early diagnosis and therapy

Cited by 94 publications

References 35 publications

Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cells

Phosphorylation of claudin-4 by PKCε regulates tight junction barrier function in ovarian cancer cells

Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas

Induction of human tumor‐associated differentially expressed gene‐12 (TADG‐12/TMPRSS3)‐specific cytotoxic T lymphocytes in human lymphocyte antigen‐A2.1–positive healthy donors and patients with advanced ovarian cancer

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