Transforming growth factor-? differentially inhibits epithelial ovarian carcinoma cells from primary and metastatic isolates without up-regulation of p21WAF1

Hurteau, Jean; Allison, Bernadette M.; Sutton, Gregory P.; Moore, David H.; Look, Katherine Y.; Hurd, William W.; Bigsby, Robert M.

doi:10.1002/(sici)1097-0142(19990415)85:8<1810::aid-cncr22>3.0.co;2-e

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…Ovarian carcinoma is thought to be a clonogenic disease in which malignant cells exfoliate from the primary tumor and disseminate throughout the peritoneal cavity. The molecular events that allow these cells to escape immunologic detection and to form metastatic peritoneal implants have not been well defined (21) .…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical staining was done on formalin‐fixed and paraffin‐embedded tissue using the ABC (avidin‐biotin‐peroxidase complex) method, which is a simple and sensitive method for localizing antigens in formalin‐fixed tissues (21) . Sections of 5‐μm thickness from at least one representative block from each tumor were deparaffinized in xylene (2 × 10 min) and then rehydrated with graded alcohol.…”

Section: Methodsmentioning

confidence: 99%

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The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy

Skírnisdóttir¹,

Seidal²,

Gerdin³

et al. 2002

Int J Gynecol Cancer

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Epithelial ovarian cancer is one of the major causes of death among women. The increasing knowledge about molecular events involved in the early stages of ovarian tumorigenesis may provide the basis for management in the future. In a series of 109 patients with epithelial carcinomas in FIGO stages IA-IIC, a number of clinicopathologic prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to the biologic factors p53, bcl-2, and bax, which are important regulators of apoptosis. Immunohistochemical techniques were used. All the patients received adjuvant chemotherapy after the primary surgery. Univariate analysis showed that expression of p53 was significantly associated with tumor grade (P = 0.014), probability of persistent disease (P = 0.016), and cancer-specific survival rate (P = 0.007). Positive bcl-2 staining was associated with endometrioid tumor subtype (P = 0.029) and a favorable tumor grade distribution (P = 0.034), but not with the survival status. The combined p53-bcl-2 expression was related to histopathologic subtype (P = 0.032), tumor grade (P = 0.011), persistent disease (P = 0.014), and risk of dying due to the disease (P = 0.039). The bax status was not a prognostic factor, but the combined p53-bax expression showed an association with FIGO stage (P = 0.014), tumor grade (P = 0.034), persistent disease (P = 0.006), and risk of dying due to the disease (P = 0.039). The combined bcl-2-bax expression was related to histopathologic subtype (P = 0.045) and tumor grade (P = 0.022). In a multivariate Cox analysis, tumor grade (P = 0.014), and p53 status (P = 0.020) were independent and significant prognostic factors with regard to the cancer-specific survival rate.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy

Skírnisdóttir¹,

Seidal²,

Gerdin³

et al. 2002

Int J Gynecol Cancer

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“…Studies of metastatic OC have, nevertheless, documented mainly a tumor-promoting effect for this pathway to date. OC cells isolated from metastases were more TGFβ-responsive than those isolated from the ovarian tumors [ 20 ]. Stromal progenitor cells isolated from OC ascites had high TGFβ expression [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…With the development of proteome analysis technology, MS greatly accelerates signaling research through high-throughput quantification [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Splice-Variant Knock-Out of TGFβ Receptors Perturbates the Proteome of Ovarian Carcinoma Cells

Catane

Moshel

Smith

et al. 2021

IJMS

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The aim of this study was to analyze the biological role of different transforming growth factor-β (TGFβ) receptor splice variants in ovarian carcinoma (OC). Specific receptor variant knockouts (KO) were prepared using the CRISPR/Cas9 genome editing system in two OC cell lines, TβRI variant 1 (TβRIv1) KO in ES-2 cells and TβRII variant 1 (TβRIIv1) KO in OVCAR-8 cells. Control and KO cells were compared by proteomic analysis, functional tests, analysis of epithelial–mesenchymal transition (EMT) drivers, and Western blot of signaling proteins. Proteomic analysis revealed significant changes in protein pathways in the KO cells. TβRIv1 KO resulted in a significant reduction in both cellular motility and invasion, while TβRIIv1 KO significantly reduced cellular motility and increased Reactive Oxygen Species (ROS) production. Both receptor variant KOs reduced MET protein levels. Of the EMT drivers, a significant decrease in TWIST protein expression, and increase in SNAIL protein and MALAT1 mRNA levels were observed in the TβRIIv1 KO compared to control. A significant decrease in JNK1 and JNK2 activation was found in the TβRIv1 KO compared to control cells. These findings provide new insight regarding the biological role of the TGFβ receptor variants in the biology and potentially the progression of OC.

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“…Studies of metastatic OC have nevertheless to date documented mainly tumor-promoting effect for this pathway. OC cells isolated from metastases are more TGFβ-responsive than those isolated from the ovarian tumors [12]. OC cells promote proliferation of omental fibroblasts via TGFβ signaling, whereas the latter promote adhesion and invasion in OC cells upon co-culturing [13].…”

Section: Discussionmentioning

confidence: 99%

TGFβ splicing and canonical pathway activation in high-grade serous carcinoma

et al. 2017

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The present study analyzed the expression and clinical role of the transforming growth factor-β (TGFβ) pathway in high-grade serous carcinoma (HGSC), with focus on malignant effusions. TGFβ1-3 and TGFβRI-III mRNA expression by qRT-PCR was analyzed in 70 HGSC effusions and 55 solid specimens (28 ovarian, 27 abdominal metastases). Protein expression of Smad2 and Smad3 and their phosphorylated forms by Western blotting was analyzed in 73 specimens (42 effusions, 13 ovarian carcinomas, 18 solid metastases). Expression was analyzed for association with anatomic site and clinical parameters, including survival. TGFβRI and TGFβRII mRNA was overexpressed in effusions and solid metastases, particularly the former, compared to that in the ovarian tumors (p < 0.001 to p = 0.05), with anatomic site-dependent expression of splice variants. Conversely, Smad2, p-Smad2, and p-Smad3 were overexpressed in solid specimens (ovarian and peritoneal) compared to those in effusions (p < 0.001 for all). In univariate survival analysis, higher TGFβRI variant 1 and TGFβRIII mRNA levels were associated with a trend for shorter overall survival in patients with post-chemotherapy effusions (p = 0.066 and p = 0.087, respectively), and the latter was an independent prognostic marker in Cox multivariate analysis (p = 0.041). Smad3 protein expression was associated with a trend for shorter overall survival in univariate survival analysis (p = 0.052). TGFβ receptor splice variant expression is anatomic site-dependent in HGSC. Elevated levels of TGFβ signaling pathway mRNAs are seen in metastatic HGSC, but are not accompanied by increased Smad expression and activation in HGSC effusions, evidence of failure to activate canonical TGFβ signaling. Assessment of the prognostic role of this pathway in HGSC effusions merits further research.

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Transforming growth factor-? differentially inhibits epithelial ovarian carcinoma cells from primary and metastatic isolates without up-regulation of p21WAF1

Cited by 7 publications

References 22 publications

The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy

The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy

Splice-Variant Knock-Out of TGFβ Receptors Perturbates the Proteome of Ovarian Carcinoma Cells

TGFβ splicing and canonical pathway activation in high-grade serous carcinoma

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