Association of D4-GDI expression with breast cancer progression.
D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis.
Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA.
Leslie A
LA
Rivera Rosado
Jaime
J
Rodriguez-Canales
Baolin
B
Zhang
D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D046888:Tissue Array Analysis; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
C569658:ARHGDIB protein, human; D014408:Biomarkers, Tumor; D020730:Guanine Nucleotide Dissociation Inhibitors; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors