Sumoylation Pathway Is Required to Maintain the Basal Breast Cancer Subtype

This study is an attempt to characterize the molecular basis for the functional differences between TFAP2A and TFAP2C. Recent findings have highlighted a critical role for the TFAP2C (AP-2γ) transcription factor in maintaining the luminal phenotype through the regulation of luminal-associated genes. Of particular interest is that the highly homologous AP-2 family member, TFAP2A (AP-2α), is expressed in luminal breast cancer but appears to have a functionally distinct role in gene regulation. There is 83% similarity between TFAP2A and TFAP2C with 76% identity in the carboxyl-half of the proteins containing the DNA binding and dimerization domains. Although the two family members appear to have complementary and overlapping roles in regulating neural crest development, they have clear functional differences with regard to regulation of ERα expression. The global genomic binding pattern for TFAP2A and TFAP2C is highly similar. Genomic binding for TFAP2A and TFAP2C in the regulatory region for luminal-associated genes further demonstrated co-localization of the two factors. On the other hand, clear functional differences exist when comparing the effect on the pattern of gene expression following knockdown of TFAP2A vs. TFAP2C. In each case, knockdown of TFAP2C resulted in an abrogation of expression (RNA and protein) of the luminal-associated gene, whereas, knockdown of TFAP2A had minimal or no effect. By contrast, a known TFAP2A target gene, CDKN1A, was responsive to TFAP2A only. 1 ChIP-Seq data for TFAP2A in human breast carcinoma cell line MCF-7. See associated publication.