Altered expression of transforming growth factor-? ligands and receptors in primary and recurrent ovarian carcinoma

Bristow, Robert E.; Baldwin, Roger A.; Yamada, Shigeki; Korc, Murray; Karlan, Beth Y.

doi:10.1002/(sici)1097-0142(19990201)85:3<658::aid-cncr16>3.0.co;2-m

Cited by 58 publications

(35 citation statements)

References 38 publications

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“…Participating in the activity of the TGF-b signalling pathway 26,27 , TGFBR1 binds to TGF-b and forms a heterodimeric complex with TGFBR2, leading to phosphorylation and activation of SMAD2 and SMAD3. Furthermore, TGFBR1 expression was found to be markedly reduced in recurrent ovarian tumours 28 . In addition, the deletion of TGFBR1* 6A/9A, which was known to be associated with risk of multiple cancers, was also reported to be associated with ovarian cancer risk 29,30 .…”

Section: Discussionmentioning

confidence: 94%

Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Chen

et al. 2014

Nat Commun

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Ovarian cancer is the leading cause of death from gynaecological malignancies worldwide. Here we perform a three-stage genome-wide association study (GWAS) in Han Chinese women to identify risk genetic variants for epithelial ovarian cancer (EOC). We scan 900,015 single-nucleotide polymorphisms (SNPs) in 1,057 EOC cases and 1,191 controls in stage I, and replicate 41 SNPs (P meta o10 À 4 ) in 960 EOC cases and 1,799 controls (stage II), and an additional 492 EOC cases and 1,004 controls (stage III). Finally, we identify two EOC susceptibility loci at 9q22.33 (rs1413299 in COL15A1, P meta ¼ 1.88 Â 10 À 8 ) and 10p11.21 (rs1192691 near ANKRD30A, P meta ¼ 2.62 Â 10 À 8 ), and two consistently replicated loci at 12q14.2 (rs11175194 in SRGAP1, P meta ¼ 1.14 Â 10 À 7 ) and 9q34.2 (rs633862 near ABO and SURF6, P meta ¼ 8.57 Â 10 À 7 ) (Po0.05 in all three stages). These results may advance our understanding of genetic susceptibility to EOC.

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Section: Discussionmentioning

confidence: 94%

Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Chen

et al. 2014

Nat Commun

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“…Similar results were obtained via RNAse protection assay in primary ovarian cancer specimens (Bartlett et al, 1997). Northern blot analysis indicated that mRNA levels of both TGF1 and TGF3 are increased in recurrent ovarian cancers (Bristow et al, 1999). Using enzyme-linked immunosorbant assay (ELISA), TGF1 levels are increased in plasma and peritoneal fluid of advanced stage ovarian cancer patients (Santin et al, 2001).…”

Section: Tgfligand Expression In Ovarian Cancersupporting

confidence: 66%

“…A more recent study reported reduced TGFRII levels which was determined via microarray analysis and validated via real-time PCR (qPCR) (Sunde et al, 2006). Via northern blot analysis, expression of TGFRI and TGFRIII was markedly reduced in recurrent ovarian tumors (Bristow et al, 1999). In an independent study, TGFRIII was notably decreased or absent in ovarian cancers at the RNA and protein levels (Hempel et al, 2007).…”

Section: Tgfreceptor Expression In Ovarian Cancermentioning

confidence: 98%

Dysregulated TGFB Signaling in Ovarian Cancer

Bauckman¹,

Campla²,

Nanjundan³

2012

Ovarian Cancer - Basic Science Perspective

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“…We show that TGF-b is abundantly secreted in the peritoneal milieu through autocrine and paracrine mechanisms. The existence of a functional TGF-b signaling pathway in OC has been documented in prior studies (Cardillo et al, 1997;Baldwin et al, 2003;Dowdy et al, 2003), the cytokine and its receptors being expressed in over 50% of ovarian tumors (Bartlett et al, 1997;Bristow et al, 1999;Abendstein et al, 2000). Loss of growth inhibitory effects of TGF-b in OC cells has been attributed in a minority of cases to TGF-b receptor I and II inactivating mutations (Lynch et al, 1998;Chen et al, 2001) or to alterations of cell signaling downstream of SMADs Hu et al, 2000;Baldwin et al, 2003).…”

Section: Discussionmentioning

confidence: 72%

Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer

et al. 2011

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Tissue transglutaminase (TG2), an enzyme involved in cell proliferation, differentiation and apoptosis is overexpressed in ovarian carcinomas, where it modulates epithelial-to-mesenchymal transition (EMT) and promotes metastasis. Its regulation in ovarian cancer (OC) remains unexplored. Here, we show that transforming growth factor (TGF)-b, a cytokine involved in tumor dissemination is abundantly secreted in the OC microenvironment and induces TG2 expression and enzymatic activity. This is mediated at transcriptional level by SMADs and by TGFb-activated kinase 1-mediated activation of the nuclear factor-jB complex. TGF-b-stimulated OC cells aggregate as spheroids, which enable peritoneal dissemination. We show that TGF-b-induced TG2 regulates EMT, formation of spheroids and OC metastasis. TG2 knock-down in OC cells decreases the number of cells harboring a cancer stem cell phenotype (CD44 þ /CD117 þ ). Furthermore, CD44 þ /CD117 þ cells isolated from human ovarian tumors express high levels of TG2. In summary, TGFb-induced TG2 enhances ovarian tumor metastasis by inducing EMT and a cancer stem cell phenotype.

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Altered expression of transforming growth factor-? ligands and receptors in primary and recurrent ovarian carcinoma

Cited by 58 publications

References 38 publications

Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women

Dysregulated TGFB Signaling in Ovarian Cancer

Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer

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