Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium

Kokawa, Katsuji; Shikone, Toshihiko; Otani, Tetsuo; Nishiyama, Rika; Ishii, Yuki; Yagi, Shusuke; Yamoto, Mareo

doi:10.1093/humrep/16.10.2211

Cited by 38 publications

(28 citation statements)

References 21 publications

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“…Goumenou et al [12] reported similar bax expression in adenomyotic and endometriotic samples, and no variation according to the phase of the menstrual cycle. Furthermore, previous studies have shown no difference in endometrial bax expression between women with and without endometriosis [27] or between eutopic and ectopic endometrium [26], whereas bax expression was higher in endometrioid carcinomas than in normal and hyperplastic endometrium [22]. We found no correlation between p53 and bax expression.…”

Section: Discussioncontrasting

confidence: 77%

Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours

et al. 2003

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Apoptosis is a physiological process by which multicellular organisms eliminate superfluous cells. Alterations in apoptosis play a key role in tumour development. The objective was to evaluate the immunohistochemical expression of p53, p21, bax, bak, fas, bcl-2 and bcl-x proteins in 10 endometriomas, 20 benign ovarian tumours (10 mucinous, 10 serous) and 30 malignant ovarian tumours (9 mucinous, 19 serous; 2 endometrioids). p53 positive cells (mean+/-SD) in endometriomas, and benign and malignant tumours were 1.9+/-3.2, 0 and 16.2+/-33.0, respectively. The difference was significant between benign tumours and endometriomas (P=0.003) but not between endometriomas and malignant tumours. P21 expression in endometriomas and benign and malignant tumours was 19.5+/-27.8, 1.7+/-6.7 and 4.1+/-8.6, respectively. Increased p21 expression was found in endometriomas compared with benign (P=0.001) and malignant (P=0.01) tumours. Bax expression was higher in endometriomas than in benign tumours (P=0.01), but no difference was found between endometriomas and malignant tumours. No difference in bak, fas, bcl-2 or bcl-x expression was observed among the groups. In endometriomas, a negative correlation was found between p53 and fas expression (P=0.04, r=0.66). Although endometriomas have histological features of benign ovarian tumours, endometriomas share with malignant ovarian tumours certain alterations in apoptosis-related proteins.

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Section: Discussioncontrasting

confidence: 77%

Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours

et al. 2003

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“…In the present study, positive correlations were found between WWOX and the antiapoptotic BCL2 gene as well as between WWOX and the BCL2/BAX ratio. Findings of a previous study demonstrated the increasing expression of the proapoptotic BAX gene and decreasing expression of the antiapoptotic BCL2 gene during progression from endometrial hyperplasia to cancer (27). Geisler et al (28) demonstrated that a higher expression level of the Bcl2 protein correlates with favorable clinicopathological variables such as well-differentiated tumor cells, reduced FIGO stage, lack of invasion into lymph node and superficial myometrial invasion (28,29).…”

Section: Discussionmentioning

confidence: 98%

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

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Abstract. Endometrial cancer is a lethal malignancy, the causes of which remain to be determined. The aim of the present study, carried out on tumor samples from 79 patients, was to evaluate the role of the WWOX tumor suppressor gene in endometrial adenocarcinoma. The expression levels of WWOX and its protein content were assessed in normal endometrium and cancer samples. Quantitative PCR was used to assess the correlation between the expression levels of WWOX and the genes involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription regulation (TP73, NCOR1). The relationship between loss of hetero zygosity (LOH) and WWOX mRNA levels was also investigated using high resolution melting. Results of the present study demonstrated a positive correlation of WWOX expression with BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX ratio. The results also showed that loss of heterozygosity at two analyzed loci of the WWOX gene is frequent in patients with endometrial cancer and that WWOX expression levels are lower in tumor samples than in normal tissue. In conclusion, WWOX may be involved in endometrial cancer.

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“…Aberrant apoptosis was present in dysfunctional uterine bleeding (Stewart et al 1999) and increasing cellular apoptosis was observed upon progression from endometrial hyperplasia through atypia to adenocarcinoma (Ioffe et al 1998). Moreover, undifferentiated and poorly differentiated endometrial carcinomas paradoxically exhibited higher apoptotic indices when compared with well-differentiated tumors; these high indices correlated inversely with prognosis (Heatley 1995, Kokawa et al 2001b). The highest rates of apoptosis were observed in the rare but aggressive papillary serous and clear cell endometrial carcinomas, characterized by late-stage presentation, extra-uterine invasion, and poor prognosis (Kokawa et al 2001a).…”

Section: Discussionmentioning

confidence: 99%

“…However, aberrant expression of Bcl-2 proteins in endometrial cancers is associated with increased malignancy and poor prognosis (Ioffe et al 1998, Ouyang et al 1998, Sakuragi et al 2002. Decreased levels of the anti-apoptotic Bcl-2 and upregulation of its pro-apoptotic partner Bax, correlate with increased apoptosis and progression from hyperplasia to malignancy in the endometrium (Chieng et al 1996, Henderson et al 1996, Kuwashima et al 1996, Saegusa et al 1996, Mozzetti et al 2000, Kokawa et al 2001b, Peiro et al 2001, Sakuragi et al 2002. PKCa has been shown to phosphorylate Bcl-2, which may be required for optimal anti-apoptotic function (Ruvolo et al 1998, Deng et al 2001.…”

Section: Discussionmentioning

confidence: 99%

Endometrial cancer cell survival and apoptosis is regulated by protein kinase C α and δ

Haughian

Jackson²,

Koterwas³

et al. 2006

Endocr Relat Cancer

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Endometrial cancer is the most common invasive gynecologic malignancy but the molecular mechanisms underlying its onset and progression are poorly understood. Paradoxically, endometrial tumors exhibit increased apoptosis, correlating with disease progression and poor patient prognosis. Endometrial tumors also show altered activity and expression of protein kinase C (PKC) isoforms, implicated in the regulation of programmed cell death; however, PKC modulation of apoptosis in endometrial cancer cells has not been investigated. We detected nine out of ten PKC isoforms in Ishikawa endometrial cancer cell lines, and demonstrated expression of both PKCa and d in human endometrial tumors. To determine the functional roles of PKCa and d in apoptosis in endometrial cancer, Ishikawa cells were treated with selective PKC inhibitors or adenoviral constructs encoding wild-type or isoform-specific, dominant-negative mutants. Apoptosis was assessed by DNA fragmentation and caspase-mediated poly-(ADP-ribose)-polymerase cleavage. The inhibition of PKCd suppressed etoposide-induced apoptosis, while overexpression of PKCd enhanced it. In contrast, inhibition of PKCa elevated basal levels of apoptosis and potentiated etoposide-induced cell death. Etoposide treatment also selectively activated PKCd, but resulted in both cytosolic translocation and decreased activity of PKCa. A fraction of PKCd also underwent caspase-dependent cleavage, in response to etoposide. Our results suggest that changes in apoptosis and PKC expression in endometrial cancer are mechanistically linked, such that PKCd is required for DNA damage-induced apoptosis, while PKCa mediates a survival response. Thus, PKCa and d expression and signaling may be important in endometrial tumorigenesis and could serve as potential prognostic indicators and/or novel targets for therapeutic intervention.

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Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma of the uterine endometrium

Cited by 38 publications

References 21 publications

Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours

Expression of apoptosis-related proteins in endometriomas and benign and malignant ovarian tumours

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Endometrial cancer cell survival and apoptosis is regulated by protein kinase C α and δ

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