Low Expression of P63 and P73 in Osteosarcoma

Park, Hye-Rim; Kim, Youn-Wha; Park, Jaehoon; Maeng, Young-Hee; Nojima, Takayuki; Hashimoto, Hiroshi; Park, Yong-Koo

doi:10.1177/030089160409000214

Cited by 18 publications

(16 citation statements)

References 34 publications

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“…P73 can induce apoptosis and cell cycle arrest by binding to p53 response gene or trans activating p53 response gene (25). p73 has low expression in OS, and the triggering of p73 dependent apoptosis in OS is controlled by the E2Fs-pRb2/p130 complex (26,27). However, no interaction between miR-663b and TP73 in OS cells has been reported previously.…”

Section: Discussionmentioning

confidence: 95%

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Shu¹,

Ye²,

Gu³

et al. 2018

BLL

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OBJECTIVE: This study aimed to investigate the exact role of miR-663b in osteosarcoma (OS) progression and further explore the underlying molecular mechanisms. MATERIALS AND METHODS: The miR-663b expression in human OS cell lines was determined by qRT-PCR, and the results suggested that miR-663b was highly expressed in human OS cells. TargetScan was used to predict the potential targets of miR-663b, and the prediction was confi rmed by dual-luciferase reporter assay. To investigate the role of miR-663b in OS, miR-663b was down-regulated in U2OS cells using miR-663b inhibitor. CCK8 and fl ow cytometry were preformed to investigate the proliferation and apoptosis of U2OS cells. Moreover, qRT-PCR and western blot analysis were performed to measure the mRNA and protein expression. RESULTS: We found that miR-663b directly targets TP73 and negatively regulates TP73 expression. MiR-663b inhibitor signifi cantly decreased the proliferation ability of U2OS cells, while the percentage of apoptotic cells was markedly increased. The level of Bcl-2 was notably inhibited by miR-663b inhibitor, while Bax expression was signifi cantly enhanced. Moreover, miR-663b down-regulation promoted p53 and p21 expression in U2OS cells. CONCLUSIONS: MiR-663b down-regulation represses proliferation and induces apoptosis in OS by targeting TP73. Therefore, we provide a potential therapeutic target for OS treatment (Fig. 6, Ref. 27). Text in PDF www.elis.sk.

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Section: Discussionmentioning

confidence: 95%

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Shu¹,

Ye²,

Gu³

et al. 2018

BLL

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“…The presence of p63 in giant cell tumor of bone was not entirely unexpected as it has been detected in osteosarcomas and in bone marrow cells. 19,20 However in those studies as RNA from the entire tissue was examined it is not known if p63 was preferentially expressed in any particular cell type. The mechanism(s) leading to p63 protein overexpression in giant cell tumor of bone is not known.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, in tumors of bone and soft tissue p63 expression has only been described in osteosarcoma, where it is postulated to contribute to the development of these tumors. 19 Bone and soft tissue neoplasms containing multinucleated giant cells represent a heterogeneous group of benign and malignant tumors. Differentiation among these tumors based on morphology alone can be challenging, particularly in instances of limited sampling, such as with needle-core biopsies.…”

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confidence: 99%

Giant cell tumor of bone express p63

Dickson

Wunder

et al. 2008

Modern Pathology

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p63 contributes to skeletal development and tumor formation; however, little is known regarding its activity in the context of bone and soft tissue neoplasms. The purpose of this study was to investigate p63 expression in giant cell tumor of bone and to determine whether it can be used to discriminate between other giant cell-rich tumors. Seventeen cases of giant cell tumor of bone were examined to determine the cell type expressing p63 and identify the isoforms present. Total RNA or cell protein was extracted from mononuclear-or giant cellenriched fractions or intact giant cell tumor of bone and examined by RT-PCR or western blot, respectively. Immunohistochemistry was used to evaluate p63 expression in paraffin embedded sections of giant cell tumor of bone and in tumors containing multinucleated giant cells, including: giant cell tumor of tendon sheath, pigmented villonodular synovitis, aneurysmal bone cyst, chondroblastoma, and central giant cell granuloma. The mononuclear cell component in all cases of giant cell tumor of bone was found to express all forms of TAp63 (a, b, and c), whereas only low levels of the TAp63 a and b isoforms were detected in multinucleated cells; DNp63 was not detected in these tumors. Western blot analysis identified p63 protein as being predominately localized to mononuclear cells compared to giant cells. This was confirmed by immunohistochemical staining of paraffin-embedded tumor sections, with expression identified in all cases of giant cell tumor of bone. Only a proportion of cases of aneurysmal bone cyst and chondroblastoma showed p63 immunoreactivity whereas it was not detected in central giant cell granuloma, giant cell tumor of tendon sheath, or pigmented villonodular synovitis. The differential expression of p63 in giant cell tumor of bone and central giant cell granuloma suggest that these two tumors may have a different pathogenesis. Moreover, p63 may be a useful biomarker to differentiate giant cell tumor of bone from central giant cell granuloma and other giant cell-rich tumors, such as giant cell tumor of tendon sheath and pigmented villonodular synovitis.

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“…They found that alpha smooth actin is strongly and diffusely expressed in mononuclear stromal cells in nonossifying fibroma and brown tumour of hyperparathyroidism. In all giant cell tumours of bone tested (19), more than 10 % of mononuclear stromal cells (MSC) showed antialpha smooth actin immunoreactivity and in 42 % of cases more than 50 % of the cells stained. In contrast, in all ABC and RG, most tumours had between 10 and 50 % of stained cells, while 65 % of CB had no more than 10 % of alpha smooth actin positive MSC.…”

Section: Utility Of P63 Ihc For a Diagnosis Of Benign Giant Cell-richmentioning

confidence: 99%

A diagnosis of giant cell-rich tumour of bone is supported by p63 immunohistochemistry, when more than 50 % of cells is stained

Paula

Vasiljevic²,

Giorgi

et al. 2014

Virchows Arch

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Some primary malignant or benign tumours of bone contain numerous multinucleated cells. These "giant cell-rich tumours of bone" have overlapping features and clinical and radiological data are needed to reach an accurate pathological diagnosis. We studied the potential contribution of p63 immunohistochemistry to the reliability of the histological diagnosis. We performed a multicentric retrospective study of 291 giant cell-rich tumours of bone which included 119 giant cell tumours of bone (GCTB), 76 aneurysmal bone cysts (ABC), 49 chondroblastomas (CB), 15 nonossifying fibromas (NOF), 10 giant cell reparative granulomas (RG) of jaws, 1 giant cell lesion of small bones, 2 hyperparathyroidism-related brown tumours (BT), 17 bone sarcomas with numerous osteoclasts and 2 malignant giant cell tumours of bone. p63 is expressed in ABC, CB, NOF, RG, BT and GCTB, but its expression in more than 50 % of mononuclear cells is strongly suggestive of a diagnosis of GCTB. In contrast, malignant GCTB were mostly negative. Our results show that p63 is expressed in a broad range of benign giant cell-rich tumours of bone, consistent with data in the recent literature, while infrequent in malignant tumours. With a cut-off 50 %, the presence of p63 positive cells is useful in supporting a diagnosis of giant cell-rich tumour of bone. However, a final diagnosis cannot be made without due consideration of all clinical/radiological and pathological data.

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Low Expression of P63 and P73 in Osteosarcoma

Abstract: Our data suggest that low expression of p63 and p73 is relatively common in osteosarcomas and might contribute to their molecular pathogenesis.

Cited by 18 publications

References 34 publications

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Giant cell tumor of bone express p63

A diagnosis of giant cell-rich tumour of bone is supported by p63 immunohistochemistry, when more than 50 % of cells is stained

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