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EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGFALPHA KO FETAL MOUSE PALATE
Citation:
Abbott, B D., H. Boyd, C R. Wood, AND G A. Held. EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGFALPHA KO FETAL MOUSE PALATE. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
EXPRESSION OF EGFR AND ITS LIGANDS IN RESPONSE TO TCDD OR RETINOIC ACID IN EGF AND TGF" KO FETAL MOUSE PALATE. Abbott, Barbara D.1; Boyd, Hadiya2; Wood, Carmen1; Held, Gary1. 1.EPA, ORD, NHEERL, RTD, US EPA, Research Triangle Park, NC, USA. 2MARC Program, NCCU, Durham, NC, USA.
Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF) are expressed in the developing palate and changes in patterns of expression are associated with cleft palate (CP) induction by retinoic acid (RA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The incidence of CP is reduced in EGF knockout (KO) mice after exposure to TCDD or RA on gestation day (GD)12. TGF KO affected CP incidence only at high doses of TCDD or after exposure to RA on GD10. The teratogenic responses in embryos lacking EGF or TGF may be related to expression of other ligands for the EGF receptor (EGFR). In the present study, EGFR, EGF, TGF, amphiregulin (AR), epiregulin (ER), heparin binding EGF (HB-EGF), and betacellulin (BTC) mRNA expression was evaluated with real time PCR. Pregnant mice were dosed with 100 mg/kg RA or 24 :g/kg TCDD on GD12 and total RNA was prepared from GD14 palates of wild type (WT), EGF KO, C57BL/6J, and TGF KO fetuses. Data is reported as cycle threshold (Ct) for each strain, treatment and gene examined. EGFR and BTC expression were significantly elevated in both EGF KO and TGF KO. In addition, in the TGF KO the expression of EGF and HB-EGF was induced relative to levels in C57. In response to either RA or TCDD, the WT palates had increased expression of EGF, HB-EGF and AR, compared to WT controls. In TGF KO, expression of ER was elevated by exposure to TCDD compared to control TGF KO. In EGF KO, TCDD or RA significantl effects on the expression of EGFR or the ligands were not detected. In summary, the EGF and TGF KO palates show upregulation of EGFR and some of it ligands. Exposure to TCDD or RA also altered regulation of the ligands in the WT and TGF KO palates. Increased expression of EGFR and some of its ligands may represent compensation for the lack of expression of EGF and TGF in the KO and may facilitate palatogenesis in the KO. Absence of these responses in the RA and TCDD exposed EGF KO may be implicated in the reduced sensitivity for CP induction. This abstract does not necessarily reflect EPA policy.