Differential gene expression of TGFβ inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue

Monica M. Reinholz, Ming Wen An, Steven Johnsen, Malayannan Subramaniam, Vera Jean Suman, James N. Ingle, Patrick C. Roche, Thomas C. Spelsberg

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)75-88
Number of pages14
JournalBreast Cancer Research and Treatment
Volume86
Issue number1
DOIs
StatePublished - Jul 2004

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Breast
Gene Expression
Genes
Neoplasms
Breast Neoplasms
Messenger RNA
Sensitivity and Specificity
Recurrence
Tumor Suppressor Genes
Real-Time Polymerase Chain Reaction
Population

Keywords

  • cancer
  • prognostic factors
  • signaling pathway
  • tumor suppressors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Differential gene expression of TGFβ inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue. / Reinholz, Monica M.; An, Ming Wen; Johnsen, Steven; Subramaniam, Malayannan; Suman, Vera Jean; Ingle, James N.; Roche, Patrick C.; Spelsberg, Thomas C.

In: Breast Cancer Research and Treatment, Vol. 86, No. 1, 07.2004, p. 75-88.

Research output: Contribution to journalArticle

Reinholz, Monica M. ; An, Ming Wen ; Johnsen, Steven ; Subramaniam, Malayannan ; Suman, Vera Jean ; Ingle, James N. ; Roche, Patrick C. ; Spelsberg, Thomas C. / Differential gene expression of TGFβ inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue. In: Breast Cancer Research and Treatment. 2004 ; Vol. 86, No. 1. pp. 75-88.
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