title: Coordinate suppression of Sdpr and Fhl1 expression in tumors of the breast, kidney, and prostate.
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), and prostate (P < 0.05). In addition, although Src can activate mitogen-activated protein kinase (MAPK) to promote tumor-cell growth, our data indicate that Src did not rely on MAPK activity to suppress the expression of Fhl1 and Sdpr in transformed cells. Thus, Src induced methylation of the promoter region of the Fhl1 gene; Src suppressed Fhl1 and Sdpr expression independent of mitogen-activated protein kinase (MAPK) activity; Fhl1 induced the expression of Sdpr in Src-transformed cells; and Fhl1 and Sdpr expression was suppressed in tumors of the breast, kidney, and prostate.
authors.affiliation: Molecular Biology Department, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jia
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shen
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jarvik
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nagele
authors.forename: Gary S
authors.initials: GS
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry*; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D050719:Crk-Associated Substrate Protein / Q000502:physiology; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D007680:Kidney Neoplasms / Q000737:chemistry*; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000032:analysis* / Q000235:genetics; D041681:NIH 3T3 Cells; D028044:Phosphate-Binding Proteins; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000737:chemistry*; D019061:src-Family Kinases / Q000502:physiology
chemical_list: C112303:CAVIN2 protein, human; D002352:Carrier Proteins; D050719:Crk-Associated Substrate Protein; C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D028044:Phosphate-Binding Proteins; D019061:src-Family Kinases