Overexpressed progesterone receptor form B inhibit invasive activity suppressing matrix metalloproteinases in endometrial carcinoma cells

Saito, Tsuyoshi; Mizumoto, Hisanobu; Tanaka, Ryoichi; Satohisa, Seiro; Adachi, Katsuya; Horie, Miyabi; Kudo, Ryuichi

doi:10.1016/j.canlet.2003.12.017

Cited by 24 publications

(5 citation statements)

References 23 publications

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“…PR expression of either one or both of the two PR isoforms was found to be reduced or absent in endometrial cancer [16-18,46], mostly lower for the higher histological grade [47-49] and inversely correlates with myometrium invasion [50,51]. Our results demonstrate that PR-A shows the exact same pattern of expression as ER-α in the gland and stroma cells, as well as in the different portions of EC specimens (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

et al. 2014

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Background70–80% of sporadic endometrial carcinomas are defined as endometrioid carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually retain expression of estrogen and progesterone receptors (ER and PR, respectively), as advanced stage, poorly differentiated tumors often lack one or both of these receptors. Well-described EC prognosis includes tumor characteristics, such as depth of myometrial invasion. Therefore, in the current study, we evaluated the expression profile of ER and PR isoforms, including ER-α, PR-A and PR–B, in correlation to EC tumor histological depth.MethodsUsing immunohistochemistry and image analysis software, the expression of ER-α, PR-A, PR–B and Ki67 was assessed in endometrial stroma and epithelial glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC specimens, and compared to 5 biopsies of non-malignant endometrium.ResultsExpression of PR-A and ER-α was found to be lower in EC compared to nonmalignant tissue, as the stromal expression was dramatically reduced compared to epithelial cells. Expression ratios of both receptors were significantly high in superficial and deep portions of EC; in non-tumoral portion of EC were close to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial glands of EC superficial and deep portions, and high in the extra-tumoral region. Elevated PR-B expression was found in stroma of EC, as well.ConclusionsThe ratio of ER-α and PR-A expression in the epithelial glands and the stroma of EC biopsies may serve as an additional parameter in the histological evaluation of EC tumor.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016

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Section: Discussionmentioning

confidence: 99%

Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

et al. 2014

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“…It has been suggested that PR-B status controls EMT in ECs. PR-B activation by progesterone resulted in tumor suppression by inhibiting cell growth and invasiveness via suppression of the expression of MMPs (1, 2, 7, and 9) and Ets1 transcription factor (Saito et al 2004). The relative overexpression of PR-B without transcriptional repression by PR-A was related to the metastatic potential in ECs (Kreizman-Shefer et al 2014).…”

Section: Steroid Hormones and Their Receptorsmentioning

confidence: 94%

“…In high grade EECs showing more widespread myometrial invasion, loss of PR was strongly associated with increased expression of CD44 (a CSC marker) and decreased expression of E-cadherin. The findings indicate that the molecular circuitries underlying EMT and cancer stemness may be closely interlinked during EEC progression (Hanekamp et al 2003, Saito et al 2004.…”

Section: Steroid Hormones and Their Receptorsmentioning

confidence: 99%

Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

Makker

Goel

2015

Endocrine-Related Cancer

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Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70-80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial-mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis -the most fatal consequence of endometrial carcinogenesis.

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“…MMPs are a family of zinc-and calcium-dependent proteolytic enzymes that are involved in ECM degradation and have been shown to play important roles in cancer progression (Singh et al, 2015) by altering cell invasion, migration, metastasis, and tumorigenesis (Llobet et al, 2008;Stetler-Stevenson, 2001;Stetler-Stevenson and Yu, 2001). Studies indicate that increased expression of two homologous MMPs, MMP-9 and MMP-2, correlates with aggressive forms of several cancers, including colorectal cancer, breast cancer, ovarian cancer, and melanoma (Mendes et al, 2005;Saito et al, 2004;Seftor et al, 2001;Zhang et al, 2005). In these cancers, MMP-9 and MMP-2 are secreted by cells, and elevated expression levels have been associated with poor prognosis in patients.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal organization and protein dynamics involved in regulated exocytosis of MMP-9 in breast cancer cells

Stephens

Osunsanmi

Sochacki

et al. 2019

Journal of General Physiology

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Altered regulation of exocytosis is an important mechanism controlling many diseases, including cancer. Defects in exocytosis have been implicated in many cancer cell types and are generally attributed to mutations in cellular transport, trafficking, and assembly of machinery necessary for exocytosis of secretory vesicle cargo. In these cancers, up-regulation of trafficking and secretion of matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme, is responsible for degrading the extracellular matrix, a necessary step in tumor progression. Using TIRF microscopy, we identified proteins associated with secretory vesicles containing MMP-9 and imaged the local dynamics of these proteins at fusion sites during regulated exocytosis of MMP-9 from MCF-7 breast cancer cells. We found that many regulators of exocytosis, including several Rab GTPases, Rab effector proteins, and SNARE/SNARE modulator proteins, are stably assembled on docked secretory vesicles before exocytosis. At the moment of fusion, many of these components are quickly lost from the vesicle, while several endocytic proteins and lipids are simultaneously recruited to exocytic sites at precisely that moment. Our findings provide insight into the dynamic behavior of key core exocytic proteins, accessory proteins, lipids, and some endocytic proteins at single sites of secretory vesicle fusion in breast cancer cells.

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Overexpressed progesterone receptor form B inhibit invasive activity suppressing matrix metalloproteinases in endometrial carcinoma cells

Cited by 24 publications

References 23 publications

Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

Tumor progression, metastasis, and modulators of epithelial–mesenchymal transition in endometrioid endometrial carcinoma: an update

Spatiotemporal organization and protein dynamics involved in regulated exocytosis of MMP-9 in breast cancer cells

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