2′,3′,4′-Trihydroxychalcone changes estrogen receptor α regulation of genes and breast cancer cell proliferation by a reprogramming mechanism

Table 1 Representative examples of the synergistic and reprogrammed genes regulated by the 2′,3′,4′-THC/E2 combination from the U2OS-ERα microarrays

Gene name	Gene symbol	Accession	2′,3′,4′- THC	E2	2′,3′,4′- THC + E2
Synergistic genes			Fold change
Tubulin, alpha 3d	TUBA3D	NM_080386.1	0.9	40.95	485.88
Otoferlin	OTOF	NM_194248.1	1.55	12.19	157.79
Keratin 19	KRT19	NM_002276.3	1.0	17.67	84.18
PRAME family member 4	PRAMEF4	NM_001009611.1	1.17	8.46	48.77
Tyrosine hydroxylase	TH	NM_000360.2	1.16	9.03	45.45
Gamma-aminobutyric acid B receptor, 2	GABBR2	NM_005458.5	1.54	3.86	41.30
Microseminoprotein, beta-	MSMB	NM_002443.2	1.14	3.06	27.84
Neurofilament, heavy polypeptide 200 kDa	NEFH	NM_021076.2	1.03	3.68	26.59
Zinc finger and SCAN domain containing 4	ZSCAN4	NM_152677.1	0.82	5.23	16.21
Methyl-CpG binding domain protein 3-like 2	MBD3L2	NM_144614.2	1.15	5.60	14.49
Reprogrammed genes
ATP-binding cassette, sub-family A (ABC1), member 3	ABCA3	NM_001089.1	1.24	1.85	53.37
Gardner-Rasheed Feline Sarcoma Viral (V- Fgr) Oncogene Homolog	FGR	NM_001042729.1	1.01	1.07	41.92
Keratin 73	K6IRS3	NM_175068.2	1.19	1.17	37.33
Cytochrome P450, family 4, subfamily F, polypeptide 11	CYP4F11	NM_021187.2	1.12	1.45	29.66
Mucin 1, cell surface associated	MUC1	NM_001044390.1	1.18	1.44	19.14
S100 calcium binding protein A9	S100A9	NM_002965.2	1.26	1.72	18.71
Potassium channel, subfamily K, member 6	KCNK6	NM_004823.1	0.98	0.96	15.88
Cystatin SN	CST1	NM_001898.2	0.93	1.48	15.38
Ubiquitin D	UBD	NM_006398.2	1.00	0.93	11.16
Neuronal guanine nucleotide exchange factor	NGEF	NM_019850.1	1.13	1.70	10.96

The synergistic genes were regulated by E2 alone and the addition of 2′,3′,4′-THC produced a greater activation than the sum of the response by E2 and 2′,3′,4′-THC alone. The reprogrammed genes were not regulated by E2 or 2′,3′,4′-THC alone, but were activated by the 2′,3′,4′-THC/E2 combination. U2OS-ERα cells were treated with 10 nM E2 or 5 μM 2′,3′,4′-THC alone or in combination for 24 h as described in the Methods. The fold change for the gene is the average of triplicate microarrays with a p-value ≤ 0.05 for each treatment

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