Estrogen and Anti-Estrogen Effects on the Growth of Human Epithelial Ovarian Cancer In Vitro

Nash, John D.; Ozols, Robert F.; Smyth, John F.; Hamilton, Thomas C.

doi:10.1097/00006250-198906000-00021

Cited by 74 publications

(48 citation statements)

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“…Conversely, OVCAR -3 cells express ERs functional for progesterone receptor induction but are defective for growth stimulation possibly due tò`p oor receptor level''. 21 In parallel to the stimulation of adenoviral receptor expression, transduction efficiency and cell -killing efficacy were increased in PEO4 and PEO1 cell lines by estradiol in a dose -dependent manner, whereas no effect of estradiol on these parameters was seen in OVCAR -3 and PEO14 cell lines (Fig 3 ). The increased transduction efficiency, and therefore the improved cell -killing efficacy, appears to be due to the enhanced expression of adenoviral receptor.…”

Section: Discussionmentioning

confidence: 91%

Coxsackievirus–adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression

et al. 2001

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The expression of coxsackievirus ± adenovirus receptor ( CAR ) and the integrins v 3 and v 5 was analyzed quantitatively ( flow cytometry ) and qualitatively ( immunocytochemistry ) in five human ovarian cancer cell lines ( PEO1, PEO4, PEO14, SKOV -3, and OVCAR -3 ) and three control cell lines ( 293, HeLa, and CHO -K1 ) . The transduction efficiencies were evaluated by adv / rsv --Gal transduction followed by X -gal staining. The effects of 17 -estradiol on cell growth, CAR and integrins v 3 / 5 expression, adenovirus transduction efficiency, and cell -killing efficacy of adv / rsv -tk plus ganciclovir were determined. The levels of CAR, integrin v 3, and integrin v 5 showed great variation between the cell lines. Whereas the expression of CAR appeared to be essential for and positively correlated with adenovirus transduction efficiency, the integrins v 3 and v 5 were not absolutely necessary for adenovirus transduction even though their presence may facilitate transduction. In PEO4 and PEO1 cells, proliferation was stimulated by 17 -estradiol in a dose -dependent manner. In PEO4 cells, and much less pronounced in PEO1 cells, this was accompanied by an increase in CAR expression. The stimulation of CAR expression was paralleled by an increased transduction efficiency resulting in an increased cell -killing efficacy. Our data suggest that the expression of CAR is one of the most important prerequisites for successful adenovirus -mediated gene therapy of ovarian cancer. Cancer Gene Therapy ( 2001 ) 8, 168 ± 175

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Section: Discussionmentioning

confidence: 91%

Coxsackievirus–adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression

et al. 2001

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“…There is now an emerging body of evidence from recent clinical (Rodriguez et al, 2001) al., 1998) that the growth of epithelial ovarian cancers may be in fact in¯uenced by estrogens. Several studies have shown that the growth of ER positive ovarian cancer cells could be stimulated by estradiol treatment and inhibited by tamoxifen in vitro (Nash et al, 1989;Pavlik et al, 1991;Langdon et al, 1990Langdon et al, , 1993Langdon et al, , 1994Galtier-Dereure et al, 1992). An increase in ERa mRNA relative to ERb expression has been shown in ovarian cancer cells as compared to normal ovaries, suggesting a potential role of ERa-regulated proteins in ovarian carcinogenesis Brandenberger et al, 1998;Rutherford et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Katsaros²,

et al. 2002

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Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of ®bulin-1 mRNA results in four di erent variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of ®bulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, ®bulin-1C and -1D are the predominant forms, whereas ®bulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coampli®cation of ®bulin-1C and -1D to study the relative expression of these ®bulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the ®bulin-1C:1D and ®bulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, ®bulin-1C mRNA was induced by estradiol in a dose-and time-dependent manner. Since others and we have previously shown an increased expression of ERa as compared to ERb in ovarian cancer cells, we investigated whether ERa or ERb is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and ®bulin-1, was infected with recombinant ERa or ERb encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERa-but not ERb-infected cells, suggesting that ®bulin-1C induction is mediated through ERa. In ovarian tumors, a trend towards a correlation between ®bulin-1C and ERa expression levels was noted. In conclusion, this study showed an increased ®bulin-1C: -1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This ®nding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERa promoted ovarian tumor progression.

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“…Estrogen-stimulated growth has been demonstrated in several cell lines characterized by an ER content greater than 23-30 fmol/mg protein (Nash et al 1989b, Langdon et al 1994b, Miller & Langdon 1997. Cell lines with lower ER concentrations appear unresponsive (Langdon et al 1994b).…”

Section: Experimental Studiesmentioning

confidence: 99%

“…As in ER-positive breast cancer models, 17-β estradiol (E2) regulates expression of the number of proteins associated with growth and invasion. On exposure to E2, the ER content of ER-positive cell lines is downregulated and the P g R receptor content is increased, both in culture and in vivo (Hamilton et al 1984, Geisenger et al 1989, Nash et al 1989b, Miller & Langdon 1997. Expression of transforming growth factor (TGF)-α is also increased and, consistent with the action of this growth factor, there is eventual downregulation of the epidermal growth factor (EGF) receptor (Simpson et al 1996, Miller & Langdon 1997.…”

Section: Experimental Studiesmentioning

confidence: 99%

Hormone therapy in epithelial ovarian cancer.

Makar¹

2000

Endocrine-Related Cancer

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Although epidemiologic studies, animal experiments and receptor studies have shown that not only normal ovaries but also many malignant ovarian tumors can be considered as endocrine related and hormone dependent, the place of hormonal therapy in the management of patients with ovarian cancer remains unsettled. Most trials of hormonal treatment in ovarian cancer have been retrospective, involved only limited numbers of patients, and lacked important patient-related data and information pertaining to tumor characteristics. In addition, a variety of hormonal preparations with different degrees of potency and in different dosages were included in these studies. A literature review shows that response to hormonal therapy even in a preterminal setting, is modest, with about 8% objective response but almost no side effects. In a similar patient setting, more toxic therapeutic agents do not yield a better response. The place of hormonal therapy in the management of patients with epithelial ovarian cancer needs more thorough evaluation in well-designed randomized trials. Endocrine-Related Cancer (2000) 7 85-93

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Estrogen and Anti-Estrogen Effects on the Growth of Human Epithelial Ovarian Cancer In Vitro

Cited by 74 publications

References 0 publications

Coxsackievirus–adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression

Coxsackievirus–adenovirus receptor expression in ovarian cancer cell lines is associated with increased adenovirus transduction efficiency and transgene expression

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Hormone therapy in epithelial ovarian cancer.

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