Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate

Cancer Science
Xun LiG S Goldberg

Abstract

The Src tyrosine kinase associates with the focal adhesion adaptor protein Cas (Crk-associated substrate) to suppress the expression of potential tumor suppressor genes. For example, Src utilizes Cas to suppress the expression of the LIM-only protein Fhl1 (four and a half LIM domains 1), in order to promote non-anchored tumor-cell growth and migration. Here, we report that the promoter region of the Fhl1 gene was methylated more in Src-transformed cells than non-transformed cells. In addition, global expression analysis indicates that Fhl1 induced expression of serum deprivation response factor (Sdpr) in Src-transformed cells. Moreover, Fhl1 and Sdpr was expressed in approximately 87% and 40% of samples obtained from non-transformed breast, 100% of samples obtained from non-transformed kidney, and over 60% of samples obtained from non-transformed prostate. In contrast, Fhl1 and Sdpr was detected in approximately 40% and 7% of matched samples from mammary carcinoma, less than 11% of matched samples from kidney carcinoma, and in less than 22% of matched samples from prostate carcinoma. These data indicate that Fhl1 and Sdpr expression was significantly reduced in tumors of the breast (P < 0.02 and P < 0.001), kidney (P < 0.01), a...Continue Reading

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