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Association of D4-GDI expression with breast cancer progression

Article type: Research Article

Authors: Rosado, Leslie A. Riveraa | Rodriguez-Canales, Jaimeb | Zhang, Baolina; *

Affiliations: [a] Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA | [b] Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Correspondence: [*] Correspondence author: Baolin Zhang, Ph.D., 29 Lincoln Dr., Bldg. 29A, Rm. 2A01, HFD-122, Bethesda, MD 20892, USA. Tel.: +1 301 827 1784; Fax: +1 301 480 3256; E-mail: Baolin.Zhang@fda.hhs.gov.

Keywords: D4-GDI, breast cancer, progression, immunohistochemistry

DOI: 10.3233/CBM-2012-0240

Journal: Cancer Biomarkers, vol. 10, no. 3-4, pp. 163-173, 2012

Published: 25 May 2012
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Abstract

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.

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