An immunochemical analysis of mdm2 expression in human breast cancer and the identification of a growth-regulated cross-reacting species p170

O’Neill, Mary; Campbell, Sandra J.; Save, Vicki; Thompson, Alastair; Hall, Peter A.

doi:10.1002/(sici)1096-9896(1998110)186:3<254::aid-path185>3.0.co;2-u

Cited by 11 publications

(12 citation statements)

References 53 publications

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“…OP46 was selected after testing with other antibodies including 2A10 and 3G5 (kindly given by AJ Levine, Rockefeller University, New York) both of which had technical or other limitations [48]. OP46 was used at a 1:80 dilution of 100 μg/ml and evaluated in the context of Hdm2 overexpressing A375 malignant melanoma cells, and negatively controlled with IgG2b, which was substituted for the primary antibody.…”

Section: Methodsmentioning

confidence: 99%

p14ARF expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2

et al. 2004

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Introduction p14 ARF stabilises nuclear p53, with a variable expression of p14 ARF mRNA in breast cancers. In vitro, nuclear p14 ARF binds Hdm2 to block Hdm2-dependent nucleocytoplasmic shuttling of p53, which is required before cytoplasmic degradation of p53. p14 ARF is negatively regulated by p53 and through p53-independent pathways. No studies have yet examined levels of p14 ARF protein expression in breast cancer and their relationship to Hdm2/p53 immunoreactivity or subcellular localisation. Previously, immunohistochemical expression of cytoplasmic p14 ARF , p53 and Hdm2 has been described. HER-2 (c-erbB2/neu) predicts prognosis and interacts with the p14 ARF /Hdm2 pathway to inactivate p14 ARF and to influence Hdm2 activity and localisation. This study examined p14 ARF and p53/Hdm2 expression and subcellular localisation by using immunohistochemistry in a series of invasive ductal breast cancers (IDCs) with concomitant ductal carcinoma in situ (DCIS), to evaluate whether findings in vitro were related to clinicopathological parameters such as HER-2 and their effect on patient outcome.

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Section: Methodsmentioning

confidence: 99%

p14ARF expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2

et al. 2004

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“…Using immunohistochemical techniques, overexpression of MDM2 protein (with or without gene amplification) has been reported in various human cancers, including breast cancer [75,96,[114][115][116][117], ovarian cancer [118,119], cervical carcinoma [120][121], endometrial carcinoma [122], choriocarcinoma [123], soft tissue sarcomas, osteosarcomas, rhabdomyosarcomas, leiomyomas, and leiomyosarcomas [88,[124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139], head and neck cancers [106,[140][141][142][143][144][145][146][147][148][149][150], lung and bronchogenic carcinomas [103][104][105][151][152]…”

Section: The Mdm2 Oncogene and Cancermentioning

confidence: 99%

MDM2 Oncogene as a Novel Target for Human Cancer Therapy

Zhang¹,

Wang²

2000

CPD

105

110

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The MDM2 oncogene was first cloned as an amplified gene on a murine double-minute chromosome in the 3T3DM cell line, a spontaneously transformed derivative of BALB/c 3T3 cells. The MDM2 oncogene has now been shown to be amplified or overexpressed in many human cancers. It also has been suggested that MDM2 levels are associated with poor prognosis of several human cancers. The most exciting finding is the MDM2-p53 autoregulatory feedback loop that regulates the function of the p53 tumor suppressor gene. The MDM2 gene is a target for direct transcriptional activation by p53, and the MDM2 protein is a negative regulator of p53. The MDM2 oncoprotein binds to the p53 protein, inhibiting p53 functions as a transcription factor and inducing p53 degradation. The p53 tumor suppressor has an important role in cancer therapy, with p53-mediated cell growth arrest and/or apoptosis being major mechanisms of action for many clinically used cancer chemotherapeutic agents and radiation therapy. Therefore, the MDM2-p53 interaction may be a target for cancer therapy. In addition, the negative regulation of p53 by MDM2 may limit the magnitude of p53 activation by DNA damaging agents, thereby limiting their therapeutic effectiveness. If the MDM2 feed-back inhibition of p53 is interrupted, a significant increase in functional p53 levels will increase p53-mediated therapeutic effectiveness. Several approaches have now been tested using this strategy, including polypeptides targeted to MDM2-p53 binding domain and antisense oligonucleotides that specifically inhibit MDM2 expression. In addition to the interaction with p53, the MDM2 protein has been found to have interactions with other cellular proteins such as pRb and E2F-1. Although the exact function and significance of these interactions are not fully understood, the p53-independent functions of MDM2 may have a role in cancer etiology and progression, indicating that the MDM2 oncogene is a potential molecular target for cancer therapy.

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“…The antigens selected for investigation were c-erbB-2 protein, oestrogen and progesterone receptors, NM23, Ki67, p53, and the p53 binding protein MDM2, each of which has been shown to be of potential prognostic significance in breast cancer. [3][4][5][6][7][8] Methods…”

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confidence: 99%

A study of interval breast cancer within the NHS breast screening programme

Cowan

Angus²,

Gray³

et al. 2000

Journal of Clinical Pathology

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Aim-To define the biological nature and malignant potential of interval cancers presenting to a breast unit within the NHS breast screening programme. Methods-112 interval cancers were compared with matched, screen detected and symptomatic cancers in terms of their radiographic, histopathological, and immunohistochemical features. Results-Interval cancers, strictly defined, showed no characteristic radiographic pattern. In terms of size, vascular invasion, lymph node status, and prognosis they were intermediate between screen detected and symptomatic cancers. Within the interval cancers there was an excess of grade 1 and grade 3 tumours, and lesions with a high Ki67 index but immunohistochemistry otherwise failed to discriminate between the three groups. Inclusion of data from false negative "interval cancers" did not significantly alter the results. Conclusions-Interval cancers are more aggressive than screen detected cancers but in general less aggressive than symptomatic cancers. However, within a heterogeneous group, occasional interval cancers are exceptionally malignant.

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An immunochemical analysis of mdm2 expression in human breast cancer and the identification of a growth-regulated cross-reacting species p170

Cited by 11 publications

References 53 publications

p14ARF expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2

p14ARF expression in invasive breast cancers and ductal carcinoma in situ– relationships to p53 and Hdm2

MDM2 Oncogene as a Novel Target for Human Cancer Therapy

A study of interval breast cancer within the NHS breast screening programme

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