Apoptosis, cellular proliferation and expression of p53 in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause

Wu, Xinhui; Blanck, Agneta; OLOVSSON, MATTS; MÖLLER, BJÖRN; FAVINI, ROBERTA; Lindblom, Bo

doi:10.1080/j.1600-0412.2000.079005397.x

Cited by 26 publications

(13 citation statements)

References 18 publications

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“…This is in agreement with previously published data [8][9][10][11]. It has been suggested that the control of growth is regulated differently in the myometrium and leiomyomas and that the proliferative activity in leiomyomas is stimulated by progesterone [6,11]. The concept of hormonal control of proliferative activity is supported by the findings that the menopause and GnRHa therapy greatly reduce the number of mitotic cells [11][12][13].…”

Section: Discussionsupporting

confidence: 81%

“…It has been suggested that progesterone may act as a growth-promoting factor in the regulation of leiomyoma growth through enhanced inhibition of apoptosis [3]. 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].…”

Section: Discussionmentioning

confidence: 80%

“…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: 99%

“…It has also been suggested that leiomyoma growth, like the growth of any tumour, might be caused by an imbalance between cell proliferation and cell death. Previous investigations on uterine leiomyomas have focused on the possi-ble role of ovarian steroids in the regulation of proliferation and apoptosis in these tumours [3][4][5][6]. It seems as if steroids influence the growth of leiomyomas by stimulating cell proliferation rather than by affecting apoptosis, and that cell proliferation is enhanced under the influence of progesterone, rather than oestrogen [6].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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View full text Add to dashboard Cite

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“…These findings are consistent with the lack of morphologic evidence of differences in degree of apoptosis within the tumors and corresponding myometria, either by examination of H&E-stained sections or by the TUNEL technique. A similar lack of difference in apoptotic indices between leiomyomas and myometrium has been observed by other authors [33].…”

Section: Discussionsupporting

confidence: 75%

Cell proliferation and apoptosis in human uterine leiomyomas and myometria

et al. 2002

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To determine the role of cell proliferation and apoptosis in uterine leiomyoma growth, we studied protein expression of two major regulatory proteins of apoptosis -- Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic) -- and two endogenous markers of cell replication - proliferating cell nuclear antigen (PCNA) and Ki-67 - in tumors and matched myometrium from premenopausal women. Conventional mitotic indices also were determined, and all proliferation data were correlated to tumor size. In situ end-labeling of fragmented DNA and routine histology were used to assess apoptosis. Our results showed that the apoptosis-regulating proteins (Bcl-2 and Bax) were expressed in the cytoplasm of the leiomyoma and myometrial smooth muscle cells throughout the menstrual cycle. Bax expression differed from Bcl-2 in that it also was found in the cytoplasm of vascular smooth muscle cells of the myometria and tumors. Both tumors and myometrial samples expressed 26-kDa and 21-kDa proteins that reacted with antibodies directed towards Bcl-2 and Bax, respectively. Apoptosis was not a prominent feature of uterine leiomyomas or myometrium. PCNA- and Ki-67-labeling and mitotic counts were significantly ( P<0.05) higher in leiomyomas than in matched myometrial samples. Proliferative activity was variable for individual tumors of the same patient and independent of tumor size. Our results suggest that altered apoptosis by overexpression of Bcl-2 or by decreased expression of Bax does not appear to be a major factor in uterine leiomyoma growth. We conclude that increased cell proliferation is the most significant contributor to growth and that the proliferative state is autonomous for each tumor in a given patient and is independent of tumor size.

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Four novel single nucleotide polymorphisms within the promoter region of p53 gene and their associations with uterine leiomyoma

Hsieh

Wang

Lin

2006

Molecular Reproduction Devel

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Dysregulated p53 expression has been implicated as a major contributor to numerous tumorigenesis. Single nucleotide polymorphisms (SNPs) within the functional consequence of the novel p53 promoter region remains obscure. Herein, we aimed to establish the extent of genetic variability within the promoter region of p53 gene as well as their association with leiomyoma susceptibility. Women were divided into two groups, leiomyoma (n = 160) and nonleiomyoma controls (n = 200). Total DNA was isolated from the peripheral blood of subjects. The DNA fragment containing p53 promoter regions (+64 approximately -404 bp) were obtained by amplification of polymerase chain reaction. The variations of DNA fragments were detected by DNA sequencing or restriction fragment length polymorphism (RFLP). Sequence alignment was used to identify sequence variations in p53 promoter regions. Genotypes were analyzed by method of RFLP. Genotypes/allelic frequencies in the leiomyoma and control groups were compared. A total of 15 sequence variations within p53 promoter region were identified, including -408 T/C, -382 A/G, -359 A/G, -325 T/C, -250 A/G, -216 T/C, -205 G/A, -198 G/A, -177 T/C, -103 A/G, -81 G/A, -71 G/A, -51 T/A, -33 A/G, and -17 T/C. Among these variations, four SNPs (-250 A/G, -216 T/C, -103 A/G, and -33 A/G) were established. Allele frequencies of -250*G/-216*C/-103*G/-33*G in the leiomyoma group and control group 6.9/5.0/5.9/3.8% and 3.8/1.8/2.3/4.0%, respectively. Two of them (-216*C and -103*G) are associated with higher leiomyoma susceptibility. We concluded that some sequence variations were observed within the promoter region of p53 gene. The SNPs of -216*C and -103*G among the identical sequence variations are associated with leiomyoma development.

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Apoptosis, cellular proliferation and expression of p53 in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause

Abstract: Our findings indicate that sex steroids influence the growth of leiomyomas by stimulating cell proliferation rather than by affecting apoptosis. The rate of cell proliferation is higher in fertile age than after menopause and appears to be enhanced under the influence of progesterone.

Cited by 26 publications

References 18 publications

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

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

Cell proliferation and apoptosis in human uterine leiomyomas and myometria

Four novel single nucleotide polymorphisms within the promoter region of p53 gene and their associations with uterine leiomyoma

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