Expression of Leukemia/Lymphoma Related Factor (LRF) in Human Breast Carcinoma

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Authors
Agrawal, Anshu
Issue Date
2008-08
Type
Dissertation
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en_US
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The pox-virus zinc finger protein (POZ-ZF), also termed leukemia/lymphoma related factor (LRF) belongs to the POK family of transcriptional repressors, which is also known as POK erythroid myeloid ontogenic factor (Pokemon), factor binding to short transcripts of HIV-1 (FBI-1), and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not been confirmed. The aim of this study was to investigate the expression of LRF and propose a mechanism for its function in human breast carcinoma. |The expression of LRF mRNA transcripts and protein in human breast biopsy tissues was quantified by RT-PCR and western blotting. All malignant breast tissues expressed significantly more LRF mRNA transcripts and total protein than the benign breast tissues. LRF expression was also observed in human colon, renal, lung, hepatocellular, mesothelioma, and thymoma carcinomas. In general, a significantly higher expression of LRF was seen in malignant tissue than in the corresponding benign or normal tissue. |LRF expression was high in four of five breast cell lines. Its expression was significantly increased in response to IGF-1, TGF-β1, and TGF-β2 but not EGF. Overexpressed LRF significantly increased TGF-βRII and Smad4 expression. It also activated and interacted with the active p65 subunit of NF-κB. Overexpressed LRF also upregulated the expression of the cyclin A, down- regulated p21CIP/WAF expression and induced cell cycle arrest in the G2 phase. Further studies are warranted to determine the malignant or proliferative role of LRF in human breast carcinoma.
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Creighton University
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