J. Cancer Mol. 2: 79-84, 2006

[Research Paper]

Two-Phased Alteration and Clinical Relevance of MTA1 and MTA1s Gene Expression: A Quantitative PCR Analysis in Breast Cancer Patients

Kung-Chia Young, Ching-Ting Huang, Shoei-Loong Lin, and Wei-Chiang Hsiao

Department of Medical Laboratory Science and Biotechnology [K.-C. Young, C.-T. Huang] and Department of Surgery [W.-C. Hsiao], College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Surgery, Chiayi Hospital, Chiayi, Taiwan [S.-L. Lin]

Abstract:

Aim: Metastasis-associated protein 1 (MTA1) and the short-form variant of MTA1 (MTA1s) have been demonstrated to modulate estrogen receptor (ER) alpha-mediated gene transactivation and signal transduction.  Overexpression of MTA1 is associated with tumor invasion and migration in several types of human cancers originated from gastrointestinal system, liver and lung.  In the present study, we tested the hypothesis that the levels of MTA1 and MTA1s expression might affect mammary carcinogenesis and clinical breast cancer characters from female patients in Taiwan.

Methods: A quantity of MTA1 and MTA1s at RNA level was determined in surgically resected specimens of 47 breast cancer tissues and paired adjacent normal tissues by real-time PCR technology.  We compared the clinical parameters and investigated for association with MTA1 and MTA1s expression.

Results: Breast tumor tissues displayed significantly declining levels of both MTA1 (P < 0.001) and MTA1s (P < 0.001) compared to the normal matched samples, with a mean down-regulation of ~ 94%.  The ratio of MTA1s/MTA1 remained constant in the paired tissues.  The MTA1 level was significantly higher in the group with tumor size > 5 cm compared to that with tumor size < 5 cm (P = 0.050) and it was also significantly higher in the group with number of metastatic lymph nodes > 4 than that without lymph node metastasis (P = 0.032).  In addition, MTA1s was significantly correlated with ER alpha expression (P < 0.001), and the amount of MTA1s in the tumors with nuclear expression of ER alpha was higher than that in the tumors without ER alpha expression (P = 0.042). 

Conclusion: Our data suggest that MTA1 and MTA1s regulate mammary carcinogenesis and breast cancer progression in Taiwanese women.

Received 3/16/06; Revised 4/4/06; Accepted 4/7/06.

¹Correspondence: Dr. Wei-Chiang Hsiao, Department of Surgery, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan. Phone: 886-06-235 3535 ext 5787. FAX: 886-06-236 3956. E-mail: chart@mail.ncku.edu.tw

²Abbreviations: ER, estrogen receptor; MTA1, metastasis-associated protein 1; MTA1s, short-form variant of MTA1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LN, lymph node.