SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens

Hua, Wenhui; Christianson, Tracy A.; Rougeot, Christian; Rochefort, Henri; Clinton, Gail M.

doi:10.1016/0960-0760(95)00187-5

Cited by 72 publications

(59 citation statements)

References 29 publications

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“…As shown in Fig. 7A, E 2 (10 K8 M/l) stimulation elicited a twofold increase of ERa-mediated reporter gene activity in control-siRNA expressing cells, which was in agreement with the previous report (Hua et al 1995). However, only Effect of LRP16 knock-down in SKOV3 cells on cell proliferation.…”

Section: Lrp16 Modulates Era-mediated Signaling Transduction In Skov3supporting

confidence: 92%

“…be observed in SKOV3 cells (Hua et al 1995). To determine whether LRP16 functions as an active ERa coactivator in SKOV3 cells as it does in estrogen-dependent ERa-positive epithelial cancer cells, we tested the effect of LRP16 expression on ERa-mediated transcription by using a 3!ERE-TATA-Luc reporter construct.…”

Section: Lrp16 Modulates Era-mediated Signaling Transduction In Skov3mentioning

confidence: 99%

“…Hence, characterizing ERa-mediated gene expression in estrogen-insensitive ovarian cancer cells might underlie the unresponsiveness of ovarian cancer to estrogen and resistance to hormonal therapy. The SKOV3 human ovarian carcinoma cells, which have functional ERa but are growth-resistant to estrogen and antiestrogens (Langdon et al 1994b, Hua et al 1995, were commonly used as an in vitro model for estrogen and antiestrogen resistant ovarian cancer (Havrilesky et al 2001, O'Donnell et al 2005.…”

Section: Introductionmentioning

confidence: 99%

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Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Tian

Wu²,

Zhao³

et al. 2009

Journal of Endocrinology

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Previously, we investigated the induction effect of LRP16 expression by estrogen (17b-estradiol, E 2 ) and established a feed-forward mechanism that activated estrogen receptor a (ERa) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ERa signaling transduction by functioning as an ERa coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E 2 -responsive BG-1 ovarian cancer cells, but was downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ERa upregulated LRP16 expression and enhanced LRP16 promoter activity in SKOV3 cells; however, this induction was blocked by estrogen stimulation. Results from chromatin immunoprecipitation experiment revealed a strong recruitment of the unliganded ERa at LRP16 promoter in the absence of estrogen; however, ERa was largely released from the DNA upon E 2 stimulation. Modulation in LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E 2 . Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response elementdependent ERa reporter gene activity and E 2 -induced c-Myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogenrepressed signaling pathway antagonizes estrogen-activated signaling transduction.

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Section: Lrp16 Modulates Era-mediated Signaling Transduction In Skov3supporting

confidence: 92%

Section: Lrp16 Modulates Era-mediated Signaling Transduction In Skov3mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Tian

Wu²,

Zhao³

et al. 2009

Journal of Endocrinology

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“…Progesterone receptors were detected in OVCAR-3 [13], but not SKOV-3 [14] cells. We suspect that the therapeutic gains on cells/tumors invoked by progesterone (both in the absence and presence of cisplatin) were related to a fluidity disorder of the plasmalemma.…”

Section: Discussionmentioning

confidence: 91%

Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts

Murdoch

Kirk

Isaak

et al. 2008

Gynecologic Oncology

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Objectives-The underlying premise of these investigations was that the lipophilic hormone progesterone, which partitions into and (at relatively high concentrations) impedes the fluid mechanics of the plasmalemma, would perturb integral associations between membrane lipids and exporter pumps that otherwise confer drug resistance. That progesterone can affect susceptibility of ovarian adenocarcinoma cells and xenografts to cisplatin was tested.Methods-The cisplatin-resistant human cell lines SKOV-3 and OVCAR-3 were treated for 24 hours with cisplatin (0.1 μg/ml) ± progesterone (0.01, 0.1 μg/ml). Cytotoxicity and platinum were measured by MTT assay and inductively coupled plasma mass spectrometry, respectively. Athymic mice were inoculated intraperitoneal (ip) with SKOV-3 cells. Cisplatin (2 mg/kg/week) ± progesterone (25 mg sustained-release pellet) regimens were initiated ip at one week (when micrometastases were present) and continued to six weeks post-xenograft. Tumor burdens, histopathology, and platinum concentrations were assessed upon necropsy at 24 hours after the final injection of cisplatin.Results-There were no significant in vitro/vivo anticancer effects of cisplatin alone. High-dose progesterone enhanced platinum accretion and induced drug toxicity in both cell lines. Tumorigenesis was suppressed by cisplatin + progesterone. The treatment synergy was related to elevated tumor platinum and morphological evidence of apoptosis.Conclusion-It appears that the addition of progesterone to ovarian cancer therapeutic modalities represents a step in improving responses.

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“…However, in advanced prostate cancer, androgen requirements are reduced or eliminated; that is, the androgen-independent phenotype (Sadar et al, 1999). The loss of steroid hormone-dependent phenotype is also observed in advanced stages of breast cancer (Glauber and Kiang, 1992), ovary cancer (Hua et al, 1995) and lymphoma (Weiss et al, 1990). Although adaptation or epigenetic changes are proposed to be involved in the transition from the steroid hormonedependent to steroid hormone-independent phenotype (Culig et al, 1994;Koivisto et al, 1997;Karan et al, 2003), the molecular mechanisms involved in the development of steroid hormone-independent phenomenon remain to be further delineated.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-317 of p52Shc mediates androgen-stimulated proliferation signals in human prostate cancer cells

2004

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SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens

Cited by 72 publications

References 29 publications

Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts

Tyrosine-317 of p52Shc mediates androgen-stimulated proliferation signals in human prostate cancer cells

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