EAAC1 Aspartate Transporter Expression in Normal, Hyperplastic and Neoplastic Human Prostate Gland
MM Desouki, MT Smith, LC Costello, RB Franklin. MUSC, Charleston, SC; Dental School, University of Maryland, Baltimore, MA
Background: It is essential for prostate glandular cells to possess a plasma membrane-associated aspartate uptake transport system to keep the high citrate concentration gradient of 40-1 between intra and extracellular compartments. We previously identified that excitatory amino acid carrier (EAAC1) plays an important role in L-aspartate transport process in prostate metabolism. The goal of the present work is to compare the expression of EAAC1 in normal, BPH and prostate adenocarcinomas (PCa).
Design: EAAC1 protein expression in prostate tissue sections were determined by IHC using anti-EAAC1 antibody. Sections prepared from archival paraffin blocks of 11 normal core biopsies, and 22 cases of PCa in which normal prostatic glands were identified in 5 cases and BPH in all cases (n=22) were investigated. The appearance of membrane-associated immuno-positivity of the glandular epithelial cells was used for scoring as: negative, no; +, < 10%; ++, 10-50% and +++, > 50% positive cells. The mean scores were analyzed by the Student's t-Test.
Results: Normal, BPH and PCa glandular epithelium exhibit immuno-positive EAAC1 staining localized mainly at cell membranes. Analysis of the cases for the presence of glands that exhibit membrane EAAC1 positivity showed that the protein is expressed in normal (16/16), BPH (21/22) and PCa (22/22). The density of expression of EAAC1 showed significant difference between normal and BPH as one group and PCa as second group (p<0.001). Acini composed of >10% positive cells reveals that normal and BPH glands exhibited this criterion in 58% (22/38) of cases compared to 91% (20/22) for the PCa.
Conclusions: The present work revealed that EAAC1 is highly expressed in malignant prostate glandular epithelium. In normal prostate, which accumulates citrate for secretion, aspartate is the source of oxaloacetic acid (OAA) for citrate synthesis. In PCa, the citrate level decreases because of increased oxidation due to loss of zinc and its inhibition of mitochondrial aconitase. Citrate is also a major source of acetyl CoA for lipid synthesis which is required for membraneogenesis and proliferation of cancer cells. The citrate used for lipid biosyntheses is not re-cycled to OAA, thus a readily available source of OAA is needed for citrate synthesis to support cell proliferation. We speculate therefore, that the EAAC1 aspartate uptake transporter is up regulated in prostate cancer cells to provide aspartate which is converted to OAA for citrate synthesis.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 102, Wednesday Morning