Expression of the mitogen-inducible gene-2 (mig-2) is elevated in human uterine leiomyomas but not in leiomyosarcomas

Kato, Kiyoshi; Shiozawa, Tanri; Mitsushita, Junji; Toda, Ayaka; Horiuchi, Akiko; Nikaido, Toshio; Fujii, Shingo; Konishi, Ikuo

doi:10.1016/j.humpath.2003.08.019

Cited by 37 publications

(39 citation statements)

References 25 publications

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“…24) but downregulated or lost in some other cancer cases (e.g., uterine leiomyosarcoma and certain cases of breast cancer; refs. 24,25). Based on these findings, we propose a model in which Mig-2 influences cancer cell invasion in an invasion modedependent fashion.…”

Section: Mig-2 Inhibits Pericellular Proteolytic Activity Of Sk-lms-1mentioning

confidence: 86%

“…These results suggest that alterations (either increase or decrease) of the Mig-2 level could potentially contribute to malignant behaviors. In a separate study, Kato et al have shown that Mig-2 expression in uterine leiomyosarcoma cells, which adopt a mesenchymal morphology, is significantly lower than that of the less invasive uterine leiomyoma cells (25). This raised an interesting possibility that Mig-2 may play a role in regulation of mesenchymal cancer cell invasion.…”

Section: Introductionmentioning

confidence: 99%

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A Suppressive Role of Mitogen Inducible Gene-2 in Mesenchymal Cancer Cell Invasion

Shi¹,

2008

Molecular Cancer Research

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Cancer cell invasion of extracellular matrix (ECM) is essential for dissemination of cancer cells and metastasis. In this study, we have investigated the role of mitogen inducible gene-2 (Mig-2, also known as kindlin-2), a focal adhesion protein whose expression is altered in several types of human cancers, in mesenchymal cancer cell invasion. Mig-2 is abundantly expressed in SK-LMS-1 leiomyosarcoma cells. The level of Mig-2, however, is considerably lower in more invasive HT-1080 fibrosarcoma cells. Overexpression of Mig-2 in HT-1080 and SK-LMS-1 cells substantially reduced their ability to invade ECM in an in vitro Matrigel invasion assay. Conversely, knockdown of Mig-2 markedly increased the invasiveness of these cells. Consistent with a suppressive role in mesenchymal cancer cell invasion, Mig-2 inhibits urokinase-type plasminogen activator (uPA) secretion and pericellular proteolysis. Overexpression of Mig-2 increased uPA accumulation at the intracellular face of cell-ECM adhesions and reduced the level of secreted uPA. Conversely, knockdown of Mig-2 reduced uPA accumulation at the intracellular face of cell-ECM adhesions and increased uPA secretion. Our results reveal an important role of Mig-2 in suppression of mesenchymal cancer cell invasion and shed new light on how altered Mig-2 expression could influence cancer cell invasion. (Mol Cancer Res 2008;6(5):715 -24)

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Section: Mig-2 Inhibits Pericellular Proteolytic Activity Of Sk-lms-1mentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

A Suppressive Role of Mitogen Inducible Gene-2 in Mesenchymal Cancer Cell Invasion

Shi¹,

2008

Molecular Cancer Research

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“…MIG2 has previously been reported to be overexpressed in uterine leiomyomas, relative to normal myometrium (23). The authors speculated that MIG2 is overexpressed on the transcriptional level, and that MIG2 could be involved in hormone-mediated growth.…”

Section: Discussionmentioning

confidence: 99%

Use of an Aggressive MCF-7 Cell Line Variant, TMX2-28, to Study Cell Invasion in Breast Cancer

Gozgit

Pentecost

Marconi

et al. 2006

Molecular Cancer Research

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An estrogen receptor -negative variant of the MCF-7 breast cancer cell line, TMX2-28, was used as a model in which to study breast cancer cell invasion. Using a reconstituted basement membrane (Matrigel) assay to evaluate cell invasion, we determined that TMX2-28 cells are more invasive than MCF-7 cells and that the invasiveness of TMX2-28 is similar to that of the aggressive MDA-MB-231 breast cancer cell line. TMX2-28 cells displayed a rounded, epithelial cell -like morphology, suggesting an amoeboid mode of cell invasion, in contrast to the mesenchymal mode of invasion characteristic of spindle-shaped, fibroblast-like MDA-MB-231 cells. Using real-time reverse transcription-PCR, we found that mitogen-inducible gene 2 (MIG2) is expressed at a 17-fold higher level in TMX2-28 cells than in nonaggressive MCF-7 cells and that MIG2 mRNA levels are low in the nontumorigenic human mammary epithelial cell line, 184. We determined that MIG2 plays a role in cell invasion by using small interfering RNA (siRNA) to suppress the expression of MIG2 mRNA levels in TMX2-28 cells. TMX2-28 cell invasion was reduced by 48% when the cells were transfected with siRNAs targeting MIG2, relative to cells transfected with siRNAs against glyceraldehyde-3-phosphate dehydrogenase. Finally, MIG2 expression was evaluated in reductive mammoplasty and breast tumor tissue. Although all 21 normal tissues from reduction mammoplasty showed immunoreactivity for MIG2, ranging from weak (62%) to strong (24%), only half of the 34 formalin-fixed breast tumors showed immunoreactivity for MIG2. Of these 17 positive cases, 10 were considered to overexpress MIG2 (moderate to strong staining). Examination of 30 frozen breast tumors supported the finding that MIG2 is overexpressed in a subset of breast cancers. We suggest that MIG2's normal regulation and function are disrupted in breast cancer. (Mol Cancer Res 2006;4(12):905 -13)

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“…Since apoptotic mechanisms have also been implicated in many types of human cancer, investigation of apoptotic and cell-cycle regulator dysregulation in uterine LMS is required to identify molecular pathways that could be involved in the development of this disease. Although the significant differential expression of apoptotic and cell-cycle regulatory factors, such as sexual hormone receptors (oestrogen receptor and progesterone receptor), B-cell lymphoma-2 (BCL2); BCL2-associted X protein (BAX); P16 inhibiting cyclin-dependent kinase 4 (P16/INK4a); P21 cyclindependent kinase inhibitor 1 (P21/CIP1); P27 kinase inhibitor protein 1 (P27/KIP1); cellular v-KIT HardyZuckerman 4 feline sarcoma viral oncogene homolog (c-KIT); mitogen-inducible gene-2 (MIG2); murine double minute 2 (MDM2); tumour protein 53 (TP53); as well as human uterine LMS growth initiation factor, have all been compared to myometrium and reported, there is no scientific evidence to show that abnormal expression of these factors directly correlates with the initiation and promotion of human uterine LMS (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). As such, the apoptotic and cellcycle regulatory protein expression profiles of human uterine LMS are not yet useful for clinical prognostic purposes.…”

Section: Psmb9/β1i-deficient Mice Exhibit Spontaneous Development Of mentioning

confidence: 99%

Molecular Pathology and Novel Clinical Therapy for Uterine Leiomyosarcoma

Hayashi

Kawano

Ichimura

et al. 2016

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Abstract. Patients with uterine leiomyosarcoma (LMS)typicallyUterine mesenchymal tumours have been traditionally divided into benign leiomyomas (LMA) and malignant leiomyosarcomas (LMS), based on cytological atypia, mitotic activity, and other criteria. Globally, uterine LMSs, which are some of the most common neoplasms in the female genital tract, are relatively rare mesenchymal tumours, having an estimated annual incidence of approximately one per 160,000 women (1). They account for approximately one-third of uterine sarcomas and 1.3% of all uterine malignancies, and are considered aggressive malignancies, with a 5-year survival rate of only 50% for patients with tumours confined to the uterus (2, 3). It is noteworthy that when adjusting for 4997 This article is freely accessible online.

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Expression of the mitogen-inducible gene-2 (mig-2) is elevated in human uterine leiomyomas but not in leiomyosarcomas

Cited by 37 publications

References 25 publications

A Suppressive Role of Mitogen Inducible Gene-2 in Mesenchymal Cancer Cell Invasion

A Suppressive Role of Mitogen Inducible Gene-2 in Mesenchymal Cancer Cell Invasion

Use of an Aggressive MCF-7 Cell Line Variant, TMX2-28, to Study Cell Invasion in Breast Cancer

Molecular Pathology and Novel Clinical Therapy for Uterine Leiomyosarcoma

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