Background: Runt-related transcription factor 3 (RUNX3) is a novel tumor suppressor gene that is frequently silenced by promoter hypermethylation in gastric cancer. In this study, we aimed to analyze the methylation status of the RUNX3 promoter in breast cancer and to evaluate the relationship between RUNX3 expression and breast carcinogenesis and prognosis. Methods: RT-PCR and Western blot were applied on 5 breast cancer cell lines, the human normal breast cell line Hs578Bst and 30 pairs of breast cancer and their matching normal breast tissues to detect mRNA and protein expression of the RUNX3 gene. Methylation-specific PCR was employed to detect the methylation status of the RUNX3 promoter. Immunohistochemical study was performed to analyze RUNX3 protein expression in 88 breast cancer tissues and 40 breast fibroadenomas. Results: The expression of RUNX3 mRNA and protein were negative in 3 breast cancer cell lines (T47D, MCF7 and SKBR3) as analyzed by RT-PCR and Western blotting. Hypermethylation of the RUNX3 promotor was identified in the T47D and MCF7 cell lines, but was not detected in SKBR3. Western blot analysis showed that the RUNX3 protein of 44 kDa was detected in 15 of 30 (50%) breast cancers. However, RUNX3 protein was detected in all normal breast tissues. Methylation was detected in 13 of the 15 tissues (86.67%) that did not express RUNX3 protein, but was never detected in any surrounding normal tissues. Immunohistochemistry results revealed that the positive rate of RUNX3 protein expression in breast cancer (35.23%) was much lower than that in breast fibroadenoma (85%). RUNX3 expression was correlated with tumor infiltration, clinical stage, lymph node metastasis and the expression of estrogen and progesterone receptor (p < 0.05), but was not related to age, tumor types and pathological grade (p > 0.05). The survival rate of the patients with RUNX3-positive expression was higher than that with RUNX3-negative expression (p < 0.05). Conclusions: The expression of RUNX3 gene is decreased in breast cancer. The RUNX3 gene may play an important role in the carcinogenesis of breast cancer. The mechanism of its inactivation may be hypermethylation of the promoter. With the increased progression of breast cancer, the expression of RUNX3 protein tends to decrease. The expression of RUNX3 protein has a definite value in judging prognosis in breast cancer.

This content is only available via PDF.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.