Gene expression signature in mouse thyroid tissue after 131I and 211At exposure

Rudqvist, Nils; Spetz, Johan; Schüler, Emil; Langen, Britta; Parris, Toshima Z.; Helou, Khalil; Forssell-Aronsson, Eva

doi:10.1186/s13550-015-0137-8

EJNMMI Research

Table 2 Top three Ingenuity canonical pathways enriched by genes regulated after ¹³¹I or ²¹¹At exposure

From: Gene expression signature in mouse thyroid tissue after ¹³¹I and ²¹¹At exposure

Canonical pathway	Nuclide	Δt (h)	D (Gy)	p value	Involved molecules^a
Calcium signalling	²¹¹At	1	0.023	0.035	DOWN: MYL1, TNNC2, TNNI2, TNNT3, TPM2
			1.4	0.001	DOWN: ACTA1, ATP2A1, ATP2A3, Calm1 (includes others), MYH1, MYH2, MYH4, MYL1, TNNC2, TNNI2, TNNT3, TPM2 UP: LETM1, PRKACA
		6	0.32	<0.0005	DOWN: ACTA1, ATP2A1, MYH1, MYL1, TNNC2, TNNI2, TNNT3, TPM2
			1.4	<0.0005	DOWN: Calm1 (includes others) UP: ACTA, ATP2A1, ATP2A3, MYH, MYH2, MYH4, RYR1, TNNC2, TNNI2, TNNT3, TPM2
		24	0.05	0.180	UP: ATP2A1, LETM1, MYH2, RYR1, TNNT3
			0.5	0.390	UP: ATP2A1, MYH2
			1.4	0.009	DOWN: ATP2A3 UP: ACTA1, ATP2A1, MYH4, TNNC2, TNNI2, TNNT3, TPM2
			11	<0.0005	DOWN: Camk2b, LETM1 UP: ACTA1, ATP2A1, ATP2A3, Calm1 (includes others), CREB3L4, MYH1, MYH2, MYH4, MYL1, RYR1, TNNC2, TNNI2, TNNT3, TP63, TPM2
			32	<0.0005	DOWN: Camk2b, LETM1 UP: ACTA1, ATP2A1, ATP2A3, CREB3L4, MYH1, MYH2, MYH4, MYL1, RYR1, TNNC2, TNNI2, TNNT3, TPM2
		168	1.8	0.027	DOWN: TNNC2, TNNI2, TNNT3 UP: MYL1
	¹³¹I	24	0.85	–	–
			8.5	<0.0005	DOWN: MEF2C UP: ACTA1, ATP2A1, MYH1, MYH4, MYL1, RYR1, TNNC2, TNNI2, TNNT3, TPM2
			17	0.071	UP: ACTA1, ATP2A1
Integrin-linked kinase signalling	²¹¹At	1	0.023	0.291	DOWN: MYL1 UP: DSP, IRS2
			1.4	<0.0005	DOWN: ACTA1, ACTB, Actn3, CCND1, ITGB6, KRT18, MYH1, MYH2, MYH4, MYL1, VIM UP: IRS2, LIMS2, SH2B2, VIM, ITGB6 UP/DOWN: PPP2R5A
		6	0.32	0.004	DOWN: ACTA1, MYH1, MYL1 UP: DSP, IRS2, RHOU
			1.4	0.001	DOWN: PPAP2B UP: ACTA1, ACTN2, Actn3, DSP, MYH1, MYH2, MYH4, RHOU
		24	0.05	0.203	UP: ACTN2, LIMS2, MYH2, RHOT2 UP/DOWN: PPP2R5A
			0.5	0.413	UP: ACTN2, MYH2
			1.4	0.001	DOWN: ACTB, CCND1, CDH1, CTNNB1, ITGB4, KRT18 UP: ACTA1, FOS, IRS2, MYH4
			11	<0.0005	DOWN: Irs3, VIM UP: ACTA1, Actn3, CDH1, CREB3L4, DSP, IRS2, ITGB4, ITGB6, MYH1, MYH2, MYH4, MYL1, KRT18
			32	<0.0005	UP: ACTA1, ACTN2, Actn3, CDH1, CREB3L4, DSP, IRS2, ITGB4, ITGB6, KRT18, MYH1, MYH2, MYH4, MYL1
		168	1.8	–	–
	¹³¹I	24	0.85	0.169	DOWN: ACTB, IRS2, PPAP2B UP: FOS
			8.5	0.001	DOWN: IRS2 UP: ACTA1, ACTN2, Actn3, CCND1, FOS, MYH1, MYH4, MYL1
			17	0.076	UP: ACTA1, CCND1
Thyroid cancer signalling	²¹¹At	1	0.023	0.291	DOWN: MYL1 UP: DSP, IRS2
			1.4	0.029	DOWN: CCND1, KLK3, NGF UP: PPARG
		6	0.32	0.040	DOWN: NGF DOWN/UP: KLK3
			1.4	0.019	UP: NGF, KLK3, RET
		24	0.05	0.490	DOWN/UP: KLK3
			0.5	0.036	DOWN: KLK3, UP: NGF
			1.4	0.004	DOWN: CCND1, CDH1, CTNNB1 UP: KLK3
			11	<0.0005	DOWN: NTRK2, NTRK3, PPARG UP: CDH1, KLK3, NGF, RET
			32	<0.0005	DOWN: NTRK2, NTRK3 UP: CDH1, KLK3, NGF, RET
		168	1.8	0.026	UP: KLK3, NGF
	¹³¹I	24	0.85	0.370	UP: PPARG
			8.5	0.100	UP: CCND1, PPARG,
			17	0.004	UP: CCND1, KLK3

DOWN and UP indicate down- and upregulation, respectively. Italics indicates no statistically significant effect on the specific canonical pathway
Abbreviations: Δt exposure time, D absorbed dose
^aIPA predicts involved molecules in the form of human proteins

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