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Differential Gene Expression of TGFβ Inducible Early Gene (TIEG), Smad7, Smad2 and Bard1 in Normal and Malignant Breast Tissue

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Abstract

TGFβ/Smad signaling pathway members are potent tumor suppressors for many types of cancers. We hypothesize that breast tumors differentially express these genes and that this expression pattern plays a role in the proliferation of breast cancer. We examined the mRNA levels of TIEG, Smad7, Smad2, and Bard1 using real-time RT/PCR in 14 normal breast, five non-invasive, 57 invasive (including 29 with outcome data), and five metastatic breast tumor tissues. TIEG and Smad7 mRNA levels were lower in non-invasive tumors compared to normal breast tissues. TIEG, Bard1, and Smad2 mRNA levels were lower in invasive cancers compared to normal breast tissues. In addition, TIEG, Smad2, and Bard1, provided discriminatory ability to potentially distinguish between normal and tumor samples, N− and N+ tumors, and N-/good (no recurrence for at least 5 years) and N-/bad (recurrence within 3 years) outcome patients. TIEG mRNA levels accurately discriminated between normal breast tissue and primary tumors with a sensitivity and specificity of 96 and 93%, respectively. TIEG, in combination with Smad2, distinguished between N+ and N− primary tumors with a sensitivity and specificity of 75 and 85%, respectively. TIEG in combination with Bard1 discriminated between N-/bad outcome from N-/good tumors with a sensitivity and specificity of 83 and 82%, respectively. Our results support the hypothesis that the differential gene expression of TIEG, Smad2, and Bard1, which are tumor suppressor genes, plays a significant role in the proliferation of breast cancer. Further investigation is necessary to validate the ability of these genes to discriminate between different populations of breast cancer patients.

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Author notes

  1. Patrick C. Roche

    Present address: Department of Scientific and Clinical Affairs, Ventana Medical Systems, Inc., Tucson, AZ, USA

Authors and Affiliations

  1. Division of Experimental Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Monica M. Reinholz & Patrick C. Roche

  2. Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN, USA

    Ming-Wen An & Vera J. Suman

  3. Departments of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Monica M. Reinholz, Steven A. Johnsen, Malayannan Subramaniam & Thomas C. Spelsberg

  4. Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA

    James N. Ingle

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  1. Monica M. Reinholz
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Correspondence to Monica M. Reinholz.

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Reinholz, M.M., An, MW., Johnsen, S.A. et al. Differential Gene Expression of TGFβ Inducible Early Gene (TIEG), Smad7, Smad2 and Bard1 in Normal and Malignant Breast Tissue. Breast Cancer Res Treat 86, 75–88 (2004). https://doi.org/10.1023/B:BREA.0000032926.74216.7d

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  • DOI: https://doi.org/10.1023/B:BREA.0000032926.74216.7d

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