Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of hematological malignancies.

Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of hematological malignancies. Research Abstract Details 

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Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of hematological malignancies. Abstract Text:

Toru Motokura,Yukari Nakamura,Hiroyuki Sato,Toru Motokura,Yukari Nakamura,Hiroyuki Sato,

BACKGROUND: 14-3-3sigma is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3sigma is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3sigma expression in patients with haematological malignancies. METHODS: We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3sigma expression with real-time RT-PCR. We also examined protein levels by Western blot analysis and DNA methylation status of the 14-3-3sigma gene by methylation-specific PCR analysis of bisulfite-treated DNA. In addition, mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression levels of 14-3-3sigma were compared with those of other cell-cycle inhibitor genes, CDKN2A and ARF. RESULTS: The expression levels of 14-3-3sigma mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3sigma mRNA was aberrantly overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3%) and rarely in acute leukemia (3 of 35, 8.6%). 14-3-3sigma protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3sigma gene was not associated with expression in hematological malignancies. Mutations of p53 were identified in 12 patients and associated with lower expression of 14-3-3sigma. The expression levels of 14-3-3sigma, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is incompatible with tumor growth. CONCLUSION: 14-3-3sigma, an epithelial cell marker, was overexpressed significantly in a subset of mature lymphoid malignancies. This is the first report of aberrant 14-3-3sigma expression in non-epithelial tumors in vivo. Since the significance of 14-3-3sigma overexpression is unknown even in epithelial tumors such as pancreatic cancers, further analysis of regulation and function of the 14-3-3sigma gene in non-epithelial as well as epithelial tumors is warranted.

Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of hematological malignancies. Publishing Authors By Initials

T Motokura,Y Nakamura,H Sato,T Motokura,Y Nakamura,H Sato,

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Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of hematological malignancies. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: BMC cancer

VOLUME: 7

Page Numbers: 217

Journal Abbreviation: BMC Cancer

ISSN: 1471-2407

DAY: 25

MONTH: 11

YEAR: 2007

Aberrant overexpression of an epithelial marker, 14-3-3sigma, in a subset of hematological malignancies. Information

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LANGUAGE: eng

NlmUniqueID: 100967800

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AFFILIATION: Department of Hematology and Oncology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. motokura@grape.med.tottori-u.ac.jp

Country: England

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MEDLINETA: BMC Cancer

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