Expression of Bcl-2, Bcl-x, Mcl-1, Bax and Bak in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause

Wu, Xinhui; Blanck, Agneta; Olovsson, Matts; Henriksen, Rudi; Lindblom, Bo

doi:10.1016/s0960-0760(01)00177-7

Cited by 33 publications

(46 citation statements)

References 34 publications

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“…This suggests possible repression of Bcl-2 expression by UPA. Indeed, in the present study, abundant and intense staining for Bcl-2 observed in untreated myomas was consistent with that revealed by the literature [7, 63-65], although it was strikingly heterogeneous throughout. However, UPA treatment did not change Bcl-2 protein expression in myomas, even after repeated intermittent UPA courses.…”

Section: Discussionsupporting

confidence: 93%

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Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Courtoy

Donnez

Marbaix

et al. 2017

Gynecol Obstet Invest

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Objective: To investigate whether ulipristal acetate (UPA) treatment modifies the expression of progesterone receptor (PR), its nuclear cofactors steroid receptor coactivator-1 (SRC1) and nuclear corepressor-1 (NCoR1), prosurvival factor B-cell lymphoma 2 (Bcl-2), and Akt in uterine myomas. Patients: Prospective study of 59 women with symptomatic myomas undergoing myomectomy. Forty-two patients were treated preoperatively with UPA; the remaining 17 were not and they served as controls. Method: Tissue microarrays were obtained from surgical specimens and immunohistochemistry was performed. Blinded quantification of expression of PR (PR-A vs. PR-B), coactivator SRC1 and corepressor NCoR1, and prosurvival factor Bcl-2, and Akt and evaluation of Akt phosphorylation levels. Results: Compared with the control group, UPA does not alter PR protein levels or expression patterns in myomas, and the PR-A/PR-B ratio was similar, as well as cytoplasmic or nuclear expression of cofactors SRC1 and NCoR1. Bcl-2 was heterogeneously expressed throughout the samples and no significant modification in expression was evidenced. No significant difference was found in Akt expression and phosphorylation between treated and untreated myomas. Conclusion: This study did not find any significant change in the expression of the studied factors in myomas after UPA exposure. In conclusion, various theories on myomas cells proposed on the basis of in vitro studies are not supported in vivo.

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Section: Discussionsupporting

confidence: 93%

“…It is overexpressed in myomas [7, 63-65], where progesterone enhances Bcl-2 protein expression [63] by direct stimulation of its gene promoter, particularly via PR-A [12]. This suggests possible repression of Bcl-2 expression by UPA.…”

Section: Discussionmentioning

confidence: 99%

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Courtoy

Donnez

Marbaix

et al. 2017

Gynecol Obstet Invest

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“…Related to sex steroid hormones, Bcl-2 protein expression in leiomyoma cells has been extensively reported [25] . In this study, we noticed that there was no significant difference in Bcl-2 expression in the leiomyoma and myometrial cells, and this is supported by data previously reported by Wu et al [3] . Gossypol induces apoptosis associated with decreased expression of Bcl-2.…”

Section: Discussionsupporting

confidence: 91%

“…Bcl-2 protein was reported to be over-expressed in leiomyomas when compared with homologous myometrium. Expression of Bcl-2 protein showed a strong correlation to ERs in leiomyoma [3,4] . Estrogen inhibits apoptosis in several cell types by inducing Bcl-2 expression [5,6] , and an anti-estrogen reagent induced apoptosis by down-regulating the expression of Bcl-2 protein [7] .…”

Section: Introductionmentioning

confidence: 90%

Involvement of Bcl-2, Src, and ERα in gossypol-mediated growth inhibition and apoptosis in human uterine leiomyoma and myometrial cells

et al. 2010

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Aim:To investigate the effect of gossypol on the growth of cultured human uterine leiomyoma and myometrial cells, the level of Bcl-2 and the activity of Src and estrogen receptor (ERα). Methods: Human uterine leiomyoma and adjacent normal myometrial cells were cultured in vitro. Both cell types were treated with a graded concentration of gossypol. Cell viability was assayed using CCK-8. Morphological change was observed with optical and electronic microscopy. Apoptosis was evaluated using TUNEL assay. Levels of Bcl-2, ERα and Src were analyzed using Western blotting. Results: Gossypol significantly inhibited growth and promoted apoptosis in cultured human uterine leiomyoma cells with the IC 50 value and its corresponding 95% confidence intervals (CI) of 6.5 (4.0-10.5), 9.0 (4.9-16.5), and 7.5 (4.0-14.1) μmol/L at 20, 40, and 60 h, respectively. Gossypol exerted inhibitory effects on the myometrial cells with the IC 50 value and its 95% CI of 49.1 (28.3-85.0), 14.5 (7.7-27.4), and 2.6 (1.2-5.6) μmol/L at 20, 40, and 60 h, respectively. Compared with control, gossypol 0.1-3.0 μmol/L markedly decreased the protein expression of Bcl-2 (P<0.05) in both leiomyoma and myometrial cells in a concentration-dependent manner, and significantly suppressed the level of phospho-Tyr416Src (P<0.05) in both cell types at 3.0 µmol/L without obvious alteration of c-Src and phospho-Tyr527Src levels (P>0.05). In addition, gossypol markedly reduced both the expression of ERα (P<0.05) at the low concentration of 0.1 µmol/L in the myometrial cells and the level of phospho-ser167ERα (P<0.05) at the high concentration of 3.0 µmol/L in the leiomyoma cells. Conclusion: Gossypol inhibits proliferation and induces apoptosis in human uterine leiomyoma and myometrial cells. It is likely that the mechanisms of action involve reducing the protein level of Bcl-2 and the activity of Src and ERα.

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“…However, in a recent study no such differences in the apoptotic index were found between leiomyomas and myometrium, or between the menstrual cycle phases [6]. However, hormonal regulation of apoptosis is likely, since it has been shown that the apoptotic index is very low after the menopause [6] and after GnRHa therapy [12], and that genes coding for Bcl-2 family proteins seem to be related to and influenced by gonadal steroids [5]. Our finding of a higher apoptotic index in the peripheral parts of uterine leiomyomas compared with the central parts probably reflects nutritive differences rather than differences in hormone levels or expression of ER and PR.…”

Section: Discussionmentioning

confidence: 93%

Different Proliferative and Apoptotic Activity in Peripheral versus Central Parts of Human Uterine Leiomyomas

Bourlev¹,

Pavlovitch²,

Stygar³

et al. 2003

Gynecol Obstet Invest

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Objective: To determine whether there are differences in proliferative and apoptotic activity and in expression of sex steroid receptors between central and peripheral parts of human uterine leiomyomas in different menstrual cycle phases. Methods: Biopsy specimens of the myometrium and peripheral and central parts of uterine leiomyomas were obtained from 15 women in the proliferative phase and 8 women in the secretory phase. Mitotic cells were detected by immunohistochemical staining for Ki67. Apoptotic cells were detected by the TUNEL method. Mitotic and apoptotic indexes were calculated. Tissue levels of oestrogen and progesterone receptors were measured using a commercial monoclonal receptor enzyme immunoassay kit. Results: During the secretory phase the mitotic index was significantly higher in the peripheral than in the central parts of the leiomyomas. During the proliferative phase the apoptotic index was significantly higher in the peripheral compared with the central parts. These differences were not reflected by differences in receptor expression. Conclusions: The results of this study suggest that the growth of a human uterine leiomyoma mainly occurs in the peripheral parts of the tumour, during the secretory phase of the menstrual cycle. The findings emphasise the importance of being consistent when taking samples for research work.

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Expression of Bcl-2, Bcl-x, Mcl-1, Bax and Bak in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause

Cited by 33 publications

References 34 publications

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Progesterone Receptor Isoforms, Nuclear Corepressor-1 and Steroid Receptor Coactivator-1 and B-Cell Lymphoma 2 and Akt and Akt Phosphorylation Status in Uterine Myomas after Ulipristal Acetate Treatment: A Systematic Immunohistochemical Evaluation

Involvement of Bcl-2, Src, and ERα in gossypol-mediated growth inhibition and apoptosis in human uterine leiomyoma and myometrial cells

Different Proliferative and Apoptotic Activity in Peripheral versus Central Parts of Human Uterine Leiomyomas

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