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Prognostic Significance of Loss-of-Heterozygosity of the CUTL1 Putative Tumor Suppressor Gene in Breast Cancers

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Annual rept. 1 Jul 1998-30 Jun 1999

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A fraction approx. 18 of spontaneous breast cancers exhibited LOH of 7q22, and the smallest deleted region included the CUTL1 gene. We found no correlation between LOH at 7q22 and tumor type or grade, ER or PR expression, nodal status, or age of onset. However, the average sizes of breast tumors with or without LOH at 7q22 were 4.99 and 2.93 cm respectively. We conclude that LOH of 7q22 will not have much prognostic value. Other results forced us to reconsider the hypothesis that CUTL1 is a candidate tumor suppressor gene. Although overexpression of the full length CDPCut protein is cytotoxic, elevated CDPCut DNA binding activity in mammary epithelial cell lines correlated with higher saturation density. Moreover, proteins shorter than the full length CDPCut protein were found to be responsible for CDPCut DNA binding activity. Shorter CDPCut protein can be generated by processing of the full length protein. In addition, our studies uncovered a novel, shorter, CDPCut mRNA that was expressed at higher levels in two breast carcinoma with lobular features. In tissue culture, overexpression of this mRNA in the MCF-12A mammary epithelial cells caused some morphological changes reminiscent of epithelial-mesenchymal transition.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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