Differential gene expression of TGF beta inducible early gene (TIEG), Smad7, Smad2 and Bard1 in normal and malignant breast tissue.
TGF beta/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.
Reinholz
Monica M
MM
Division of Experimental Pathology, Department of Biochemistry, Mayo Clinic College of Medicine, Rochester, MN, USA. reinholz.monica@mayo.edu
An
Ming-Wen
MW
Johnsen
Steven A
SA
Subramaniam
Malayannan
M
Suman
Vera J
VJ
Ingle
James N
JN
Roche
Patrick C
PC
Spelsberg
Thomas C
TC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D051765:Early Growth Response Transcription Factors; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein; D051906:Smad7 Protein; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C497782:SMAD2 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051906:Smad7 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases