Effects of 17?-estradiol on c-MYC and c-Ha-RAS expression in the liver of ovariectomized female rats

Servais, Patricia; Galand, Paul

doi:10.1016/0309-1651(90)91162-w

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…Thus the reported increase in volume and number of hepatocytes supports the view that estrogens stimulate cell proliferation in the liver (10, 12, 41) and is in line with the well-established role of synthetic estrogens as tumor-promoting factors eventually resulting in liver adenoma (7, 10, 14). A possible mechanism suggested recently (12) involves increased levels of c-myc and c-Ha-ras transcripts in EE-treated rat hepatocytes and is compatible with the widely accepted role of these proto-oncogenes in proliferative competence for c-myc and in progression toward DNA synthesis and mitosis for c-ras (12,42,43).…”

Section: I)iscztssionmentioning

confidence: 99%

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Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: A stereological analysis

et al. 1992

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Structural alterations of liver parenchyma caused by ethinylestradiol, a synthetic estrogen known to induce cholestasis and to act as a tumor promoter factor, were investigated. Male rats treated with 17 alpha-ethinylestradiol (5 mg/kg body weight for 5 days) were compared with controls (n = 5 each). After perfusion fixation and systematic random sampling, paraffin sections, semithin sections and thin sections were examined observing standard stereological techniques. Ethinylestradiol treatment induced an increase in liver volume by 65% (p less than 0.001), which was caused more by hypertrophy (volume of singular hepatocyte +35%, p less than 0.001) than by hyperplasia (number of hepatocytes +23%, p less than 0.001). A decrease in sinusoidal membrane surface density (-43%, p less than 0.005) associated with a decrease in sinusoidal microvillar volume density (-50%, p less than 0.005) were both compensated for by the increase in liver volume. No canalicular alterations were observed. Thus changes in hepatocytes detectable with stereological techniques affect the sinusoidal pole where decreased sinusoidal membrane surface is associated with or reflects a substantial loss of membrane phospholipids. The increased liver volume may constitute an adaptive response compensating for the relative decrease in sinusoidal membrane surface and displays characteristics comparable to those of preneoplastic hepatocytes.

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Section: I)iscztssionmentioning

confidence: 99%

“…One step in the multistage process of tumorigenesis may be increased cell proliferation (101, which is reflected in adenoma patients by diffuse, tumorindependent enlargement of the liver (11). Indeed, EE has been demonstrated in rats to increase the mitotic activity of hepatocytes (12,13) and to promote tumorigenesis ( 14).…”

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confidence: 99%

Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: A stereological analysis

et al. 1992

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“…The 2 treatments provoke the same decrease in the activity of liver 2-5 synthetase (Smekens et al, 1986), an enzyme the activity of which is known to drop when quiescent cells are stimulated to proliferate (Krishnan and Baglioni, 1981). They also induce similar rises in c-myc expression in the liver, whereas only PH significantly increased that of c-ras (Servais and Galand, 1990). In view of the indications that the role of c-rnyc expression is on the Go-GI transition and that of c-ras on cell-cycle progression (Fausto and Shank, 1983;Mulcahy et al, 1985;Kaczmarek et al, 1985;Einat et al, 1985), this also agrees with the view that PH and E2 similar effects on the induction of proliferative competence, but (as reflected in the much lower SLI values reached with E2) not on the rate of progression in the cell cycle.…”

Section: Discussionmentioning

confidence: 84%

“…These pre-treatments were also applied 1 hr or 24 hr before administration of the carcinogen. The time of 24 hr was chosen on the basis of our previous work showing that this corresponded to the peak in the weak proliferative response of the hepatocytes after E2 treatment (Smekens et al, 1986;Servais and Galand, 1990). The time of 1 hr corresponded to the early "pre-replicative" phase and to the early events, such as nuclear translocation of the receptor, in estrogenic stimulation.…”

Section: Experimental Protocolmentioning

confidence: 99%

Increased yield in GST‐P‐positive liver pre‐neoplastic foci induced by dena or enu in rats pre‐treated with estradiol or tamoxifen

Servais¹,

Galand²

1993

Intl Journal of Cancer

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We investigated the mechanisms by which partial hepatectomy (PH) increases the ability of chemical hepatocarcinogens to induce pre-neoplastic liver foci. Comparison of the effects of pre-treatment with PH, estradiol (E2) or tamoxifen (TAM) on the yield in glutathione-S-transferase(GST-P)-positive preneoplastic foci in rat liver induced by subsequent treatment with ethylnitrosourea (ENU) or diethylnitrosamine (DENA) showed that pre-treatment with E2 increased the yield in foci induced by subsequent treatment with ENU or DENA, as compared with that in animals not pre-treated, the increase being of similar magnitude with either carcinogen. Compared with that of PH, the effect of the hormone was much more pronounced than would be expected from the relative mitogenic effect of the hormonal and surgical pre-treatments if the mitotic rate were the cause. On the other hand, the average volume of pre-neoplastic liver lesions in rats treated with ENU or DENA was 2.5 to 5.0 times higher than in rats not pretreated whenever PH was included in the pre-treatment, whereas it was not affected by any other pre-treatment.

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“…In the rat uterus, estradiol has been shown to directly stimulate expression of the c-myc proto-oncogene resulting in increased mitotic activity (Murphy et al, 1987). The molecular activity of estradiol is not clear, but in general estradiol can stimulate the expression of genes involved in the Go/G, transition of the cell cycle (c-fos, c j u n , and c-myc; Persico et al, 1990;Weisz et al, 1990) as well as genes that then promote the G,/S phase transition (c-rus; Servais and Galand, 1990). In vertebrates, progesterone exerts a significant influence over the "estrogen-responsiveness" of various tissue types (Clarke and Sutherland, 1990).…”

Section: Introductionmentioning

confidence: 99%

Effect of estradiol and progesterone on c‐myc expression in the sea star testis and the seasonal regulation of spermatogenesis

Marsh

Walker

1995

Molecular Reproduction Devel

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Analysis of the expression of cell cycle control genes provides a sensitive assay for mitotic and meiotic progression under experimental conditions. Transcription of the c-myc proto-oncogene and thymidine incorporation into DNA were both used to assay the mitogenic effects of estradiol and progesterone on the testicular germinal epithelium of the starfish Asterias vulgaris. Experimental in vitro studies during the annual spermatogenic cycle show that testes are not sensitive to mitotic stimulation by estradiol alone, whereas progesterone alone is mitotically inhibitory. The germinal epithelium can only be mitotically stimulated by estradiol after pretreatment with progesterone. The net increase in mitotic activity following a progesterone to estradiol transfer is dependent on the length of progesterone pretreatment. Overall, the seasonal pattern of testicular estradiol and progesterone levels evident in field populations of A. vulgaris (Hines et al., 1992a: Endocrinology 100:1468-1471) do not appear to be responsible for initiating spermatogonial mitosis at the onset of the annual spermatogenic cycle. Expression rates of the c-myc proto-oncogene are substantially more sensitive than thymidine incorporation in quantifying mitotic activity. Measuring proto-oncogene expression provides an ideal experimental approach to investigations of the regulatory mechanisms that control growth and reproduction in marine organisms.

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Effects of 17?-estradiol on c-MYC and c-Ha-RAS expression in the liver of ovariectomized female rats

Cited by 6 publications

References 29 publications

Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: A stereological analysis

Ethinylestradiol increases volume and decreases sinusoidal membrane surface in the rat liver: A stereological analysis

Increased yield in GST‐P‐positive liver pre‐neoplastic foci induced by dena or enu in rats pre‐treated with estradiol or tamoxifen

Effect of estradiol and progesterone on c‐myc expression in the sea star testis and the seasonal regulation of spermatogenesis

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