Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Tsuji, Kazuhiko; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Yamagami, Wataru; Nomura, Hiroyuki; Susumu, Nobuyuki; Aoki, Daisuke

doi:10.3892/ijo.2012.1384

Cited by 31 publications

(35 citation statements)

References 37 publications

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“…Women with pre-invasive atypical hyperplasia or early stages of endometrial cancers without myometrial invasion showed high response rates (70–90%) to progestin treatment [46]. The advanced stage or recurrent cancers are 20–30% responsive to progestins [47, 48]. Progestin preparations are used effectively to treat endometrial cancer.…”

Section: Discussionmentioning

confidence: 99%

Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway

et al. 2016

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Nestin, an intermediate filament protein and a stem cell marker is expressed in several tumors. Until recently, little was known about the expression levels and the role of Nestin in endometrial cancer. Compared to the immortalized endometrial epithelial cell line EM-E6/E7-TERT, endometrial cancer cell lines express high to moderate levels of Nestin. Furthermore, endometrial tumors and tumor cell lines have a cancer stem-like cell subpopulation expressing CD133. Among the cancer lines, AN3CA and KLE cells exhibited both a significantly higher number of CD133+ cells and expressed Nestin at higher levels than Ishikawa cells. Knockdown of Nestin in AN3CA and KLE increased cells in G0/G1 phase of the cell cycle, whereas overexpression in Ishikawa decreased cells in G0/G1 phase and increased cells in S-phase. Nestin knockdown cells showed increased p21, p27, and PNCA levels and decreased expression of cyclin-D1 and D3. In contrast, Nestin overexpression revealed an inverse expression pattern of cell cycle regulatory proteins. Nestin knockdown inhibited cancer cell growth and invasive potential by downregulating TGF-β signaling components, MMP-2, MMP-9, vimentin, SNAIL, SLUG, Twist, N-cadherin, and upregulating the epithelial cell marker E-cadherin whereas the opposite was observed with Nestin overexpressing Ishikawa cells. Nestin knockdown also inhibited, while overexpression promoted invadopodia formation and pFAK expression. Knockdown of Nestin significantly reduced tumor volume in vivo. Finally, progesterone inhibited Nestin expression in endometrial cancer cells. These results suggest that Nestin can be a therapeutic target for cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway

et al. 2016

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“…DIE, a fourth-generation progestin, was used in a contraceptive pill and in hormone replacement therapy [14]. Sasagawa et al [10] mentioned that DIE had a good specificity to progesterone receptor compared to other progestins.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia

Uysal

Açmaz²,

Madendağ³

et al. 2017

Gynecol Obstet Invest

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Aim: The aim of the study was to compare the effectiveness of dienogest (DIE), depo medroxyprogesterone 17-acetate (MPA), and micronized progesteron (MP) regimens for treatment of simple endometrial hyperplasia (EH) without atypia. Methods: One hundred and twenty premenopausal patients aged between 35 and 55, with simple EH without atypia, were offered 3 types of progestins (MPA, MP, and DIE) and were randomized to one of them. After 6 months of treatment, patients were reevaluated. The efficacy of different progestins in treatment of EH was compared with regard to resolution and regression rates. We classified the terms of resolution and regression as “complete response” and persistence as “no response”. Results: A total of 99 patients continued the study (31 in MP, 35 in MPA, and 33 in the DIE group). None of the results of endometrial pathology were progressed to atypia or complex hyperplasia. The complete response resolution rate was 93.5% in the MP, 88.5% in the MPA, and 96.9% in the DIE group. The highest complete response rate was in the DIE group, although there was no statistically significant difference between groups (p = 0.39). The efficacy of progestins was similar between the groups. Conclusion: DIE is an effective and convenient method for thinning the endometrium.

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“…High response rates (70-90%) are often observed for women with pre-invasive atypical hyperplasia or early stages of endometrial cancers without myometrial invasion (Kaku, et al 2001; Ushijima, et al 2007). Yet, the efficacy of progestins declines to modest response rates (15-25%) when used for cases of advanced or recurrent cancer (Banno, et al 2012) and more than 30% of patients with well-differentiated, hormone-dependent Type I tumors will fail to respond (Shao 2013). The mechanisms that result in the progression from progestin sensitivity to the hormone refractory state, or “progesterone resistance”, are poorly understood.…”

Section: Uterusmentioning

confidence: 99%

Progesterone action in breast, uterine, and ovarian cancers

Diep¹,

Daniel²,

Mauro³

et al. 2015

Journal of Molecular Endocrinology

169

152

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Progesterone and progesterone receptors (PR) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the uterus and protects the ovary from neoplastic transformation. Progesterone-dependent actions and associated biology in diverse tissues and tumors are mediated by two progesterone receptor isoforms, PR-A and PR-B. These isoforms are subject to altered transcriptional activity or expression levels, differential cross-talk with growth factor signaling pathways, and distinct post-translational modifications and cofactor binding partners. Herein, we summarize and discuss the recent literature focused on progesterone and PR isoform-specific actions in breast, uterine, and ovarian cancers. Understanding the complexity of context-dependent PR actions in these tissues is critical to developing new models that will allow us to advance our knowledge base with the goal of revealing novel and efficacious therapeutic regimens for these hormone-responsive diseases.

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Progestin therapy for endometrial cancer: The potential of fourth-generation progestin (Review)

Cited by 31 publications

References 37 publications

Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway

Nestin suppression attenuates invasive potential of endometrial cancer cells by downregulating TGF-β signaling pathway

The Efficacy of Dienogest in the Treatment of Simple Endometrial Hyperplasia without Atypia

Progesterone action in breast, uterine, and ovarian cancers

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