7071

KLF10

EGR-alpha|EGRA|TIEG|TIEG1;Kruppel-like factor 10;KLF10;Kruppel-like factor 10

Krueppel-like factor 10|TGFB-inducible early growth response protein 1|early growth response-alpha|transforming growth factor-beta-inducible early growth response protein 1|zinc finger transcription factor TIEG

8q22.2

protein-coding

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.