Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor alpha pathway

We have used a newly described method of meta-analysis of multiple cancer studies within the Oncomine database, focusing here predominantly upon breast cancer studies. We demonstrate that ERα and GATA3 reciprocally have the highest overlap with one another. Furthermore, we show that when both coexpression meta-analysis lists for ERα and GATA3 are compared there is a significant overlap between both and, like ERα, GATA3 coexpresses with ERα pathway partners such as pS2 (TFF1), TFF3, FOXA1, BCL2, ERBB4, XBP1, NRIP1, IL6ST, keratin 18(KRT18) and cyclin D1 (CCND1). Moreover, as these data are derived from human tumour samples this adds credence to previous cell-culture or murine based studies.GATA3 is hypothesized to be integral to the ERα pathway given the following: (1) The large overlap of coexpressed genes as seen by meta-analysis, between GATA3 and ERα, (2) The highest coexpressing gene for GATA3 was ERα and vice-versa, (3) GATA3, like ERα, coexpresses with many well-known ERα pathway partners such as pS2.While GATA3 has most intensively been studied in the immune system [1] GATA3 is also expressed in other biological environments such as the human endometrium epithelial cells, where levels are regulated in a cyclic manner [2]. GATA3 levels are also considered a good prognostic biomarker in breast tumours. Specifically, in the luminal A subtype of breast cancer GATA3 has both a favorable prognostic outcome, and the highest ERα and GATA3 expression of all breast tumours [3]. Consistent with this, basal-like tumours have the lowest GATA3 expression and the worst prognosis. GATA3 has also been shown in murine models to be essential to the development and maintenance of mammary luminal cells [4,5]. There is also tentative data showing that different polymorphisms of the GATA3 gene may associate with differential susceptibility to breast cancer [6].GATA3 levels have previously been correlated with expression of ERα [7] and both were shown to reciprocally regulate one an