Endocrine Factors in Common Epithelial Ovarian Cancer*

Rao, B. Ramanath; Slotman, B.J.

doi:10.1210/edrv-12-1-14

Cited by 199 publications

(116 citation statements)

References 132 publications

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“…As hormone-sensitive cancer, a large subset of ovarian cancers is associated with the deregulation of ERα or AR (Rao et al, 1991;Chan et al, 2008). Our study demonstrated that ATAD2 is overexpressed in ovarian cancers.…”

Section: Discussionmentioning

confidence: 53%

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Wan¹,

Zhang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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The purpose of this study was to explore the expression of ATAD2 in ovarian tumor tissue as well as its relationship with degree of malignancy. Tumor tissue from 110 cases of ovarian cancer was collected in accordance with the Declaration of Helsinki for evaluation of ATAD2 expression iimmunohistochemistry, quantitative PCR (qPCR) and Western blotting. The correlation between the ATAD2 expression and and the prognosis of ovarian cancer was evaluated by Cox regression model. In addition, HO-8910 and OVCAR-3 cells were transfected with two siRNAs targeting ATAD2. Cell viability was evaluated with MTT assay, and cell migration by transwell migration assay. ATAD2 was shown to be highly expressed in 65.5% (72/110) of ovarian cancer cases, both at transcriptional and protein levels. Moreover, highly expression was positively correlated with degree of malignancy. Knock-down of ATAD2 in HO-8910 and OVCAR-3 cells was found to reduce cell migration. In addition, follow-up visits of the patients demonstrated that the 5-year survival rate was lower in patients with high expression of ATAD2. Our study suggested that ovarian tumor tissue may have highly expressed ATAD2, which is associated with tumor stage, omentum-metastasis, ascites and CA-125. Increased ATAD2 may play important roles in tumor proliferation and migration. ATAD2 could serve in particular as a prognostic marker and a therapeutic target for ovarian cancer.

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Section: Discussionmentioning

confidence: 53%

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Wan¹,

Zhang²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Approximately 40 -60% of human ovarian cancers express nuclear hormone receptors such as ER␣ (and to a lesser extent, ER␤) (74,75). Recent results from three large prospective studies indicate that the risk of ovarian cancer incidence and mortality is closely associated with the activation of nuclear hormone receptors (in particular, ER␣) (76).…”

Section: Discussionmentioning

confidence: 99%

“…After an 18-h incubation at 37°C in a humidified 95% air and 5% CO 2 atmosphere, cells on the upper side of the filter were removed by wiping with a cotton swap. Cell migration processes were determined by measuring the cells that migrated to the lower side of the polycarbonate filters by standard cell number counting methods as described previously (74,75). The CD44-specific cell migration was determined by subtracting nonspecific cell migration (i.e.…”

mentioning

confidence: 99%

Hyaluronan-CD44 Interaction with IQGAP1 Promotes Cdc42 and ERK Signaling, Leading to Actin Binding, Elk-1/Estrogen Receptor Transcriptional Activation, and Ovarian Cancer Progression

Bourguignon

Gilad

Rothman

et al. 2005

Journal of Biological Chemistry

155

127

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In this study, we have examined the interaction of hyaluronan (HA)-CD44 with IQGAP1 (one of the binding partners for the Rho GTPase Cdc42) in SK-OV-3.ipl human ovarian tumor cells. Immunological and biochemical analyses indicated that IQGAP1 (molecular mass of ϳ190 kDa) is expressed in SK-OV-3.ipl cells and that IQGAP1 interacts directly with Cdc42 in a GTPdependent manner. Both IQGAP1 and Cdc42 were physically linked to CD44 in SK-OV-3.ipl cells following HA stimulation. Furthermore, the HA-CD44-induced Cdc42-IQGAP1 complex regulated cytoskeletal function via a close association with F-actin that led to ovarian tumor cell migration. In addition, the binding of HA to CD44 promoted the association of ERK2 with the IQGAP1 molecule, which stimulated both ERK2 phosphorylation and kinase activity. The activated ERK2 then increased the phosphorylation of both Elk-1 and estrogen receptor-␣ (ER␣), resulting in Elk-1-and estrogen-responsive element-mediated transcriptional up-regulation. Down-regulation of IQ-GAP1 (by treating cells with IQGAP1-specific small interfering RNAs) not only blocked IQGAP1 association with CD44, Cdc42, F-actin, and ERK2 but also abrogated HA-CD44-induced cytoskeletal function, ERK2 signaling (e.g. ERK2 phosphorylation/activity, ERK2-mediated Elk-1/ER␣ phosphorylation, and Elk-1/ ER␣-specific transcriptional activation), and tumor cell migration. Taken together, these findings indicate that HA-CD44 interaction with IQGAP1 serves as a signal integrator by modulating Cdc42 cytoskeletal function, mediating Elk-1-specific transcriptional activation, and coordinating "cross-talk" between a membrane receptor (CD44) and a nuclear hormone receptor (ER␣) signaling pathway during ovarian cancer progression.Ovarian cancer cells are characterized by their ability to freely invade the peritoneal cavity, which is consistent with the well known aggressiveness and high morbidity rate of ovarian tumors (1-3). A number of studies have aimed at identifying specific molecule(s) expressed in ovarian carcinomas that correlate with tumor cell invasive behaviors. Among such candidate molecules is CD44 (a major hyaluronan (HA) 1 receptor) (4), which belongs to a family of multifunctional transmembrane glycoproteins expressed in ovarian tumor cells and carcinoma tissues (5-9). CD44 has been found to interact with HA at the N terminus of its extracellular domain (10 -12). Ovarian cancer cells express CD44 isoforms that cause very strong cell adhesion to HA-enriched peritoneal mesothelium (8,9,13,14). A significant reduction in tumor implants has been found to occur in nude mice 5 weeks after intraperitoneal injection of ovarian cancer cells incubated with anti-CD44 antibody compared with injected cells pretreated with antibodies against other cell-surface proteins (8, 9). These findings suggest that CD44 interaction with HA may be one of the important requirements for the peritoneal spread of ovarian cancer. However, the cellular and molecular mechanisms controlling the ability of CD44-positive ovarian tumor cells to und...

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“…Sex steroid hormones have been implicated in the aetiology and/or progression of some epithelial ovarian cancers. Both oestrogen (ER) and progesterone receptors (PR) have been reported in human epithelial ovarian cancer (Rao and Slotman, 1991;Akahira et al, 2002). In endometrial and breast carcinomas, steroid hormone receptor status correlates well with response to hormonal manipulation and prognosis (McGuire, 1978;Benraad et al, 1980;Ehrlich et al, 1981;Kaupilla, 1984).…”

mentioning

confidence: 99%

“…In endometrial and breast carcinomas, steroid hormone receptor status correlates well with response to hormonal manipulation and prognosis (McGuire, 1978;Benraad et al, 1980;Ehrlich et al, 1981;Kaupilla, 1984). However, in epithelial ovarian carcinoma, the prognostic significance of tumour ER status among patients still remains controversial (Bizzi et al, 1988;Masood et al, 1989;Sevelda et al, 1990;Rao and Slotman, 1991;Hempling et al, 1998).…”

mentioning

confidence: 99%

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer

Aoki

Suzuki

et al. 2004

Br J Cancer

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Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription -polymerase chain reaction (RT -PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERa. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERa were evaluated by RT -PCR in 22 cases. The expression for EBAG9 and ERa was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P ¼ 0.0402) and advanced disease (P ¼ 0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P ¼ 0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (Po0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERa mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERa expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.

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Endocrine Factors in Common Epithelial Ovarian Cancer*

Cited by 199 publications

References 132 publications

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

Hyaluronan-CD44 Interaction with IQGAP1 Promotes Cdc42 and ERK Signaling, Leading to Actin Binding, Elk-1/Estrogen Receptor Transcriptional Activation, and Ovarian Cancer Progression

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer

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