TY - JOUR
T1 - Acid exposure activates the mitogen-activated protein kinase pathways in Barrett's esophagus
AU - Souza, Rhonda F.
AU - Shewmake, Kenneth
AU - Terada, Lance S.
AU - Spechler, Stuart Jon
N1 - Funding Information:
Supported by the Office of Medical Research, Department of Veterans Affairs, Dallas, Texas; the Glaxo Wellcome Institute for Digestive Health (to R.F.S.), the National Institutes of Health (grants HL61897 and HL52591 to L.S.T.), and the American Heart Association (to L.S.T.). Dr. Terada is an Established Investigator of the American Heart Association.
PY - 2002
Y1 - 2002
N2 - Background & Aims: To explore mechanisms whereby acid reflux might contribute to carcinogenesis in Barrett's esophagus (BE) we studied: (1) the effects of acid on the mitogen-activated protein kinase (MAPK) pathways, cell proliferation, and apoptosis in a Barrett's adenocarcinoma cell line (SEG-1); and (2) the ability of acid to activate the MAPK pathways in vivo in patients with BE. Methods: SEG-1 cells were exposed to acidic media for 3 minutes, and the activities of 3 MAPKs (ERK, p38, and JNK) were determined. Proliferation was assessed using flow cytometry; cell growth and apoptosis were assessed using cell counts and an apoptosis ELISA assay. MAPK activation was studied in biopsy specimens taken from patients with BE before and after esophageal perfusion for 3 minutes with 0.1N HCI. Results: Acid-exposed SEG-1 cells exhibited a significant increase in proliferation and total cell numbers, and a significant decrease in apoptosis. These effects were preceded by a rapid increase in the activities of ERK and p38, and a delayed increase in JNK activity. PD 98059 abolished the acid-induced increase in GO/G1 and decrease in subGO phases of the cell cycle. Both SB 203580 and DN-JNK 1/2 inhibited the acid-induced progression from GO/G1 to G2/M. The acid-induced decrease in apoptosis was abolished by inhibition of either ERK or p38. In the patients, acid exposure significantly increased the activity of p38 in the metaplastic epithelium. Conclusions: Acid increases proliferation and survival, and decreases apoptosis in SEG-1 cells by activating the MAPK pathways. Acid also activates the MAPK pathways in BE in vivo. These findings suggest that acid might contribute to carcinogenesis in BE through activation of MAPK pathways.
AB - Background & Aims: To explore mechanisms whereby acid reflux might contribute to carcinogenesis in Barrett's esophagus (BE) we studied: (1) the effects of acid on the mitogen-activated protein kinase (MAPK) pathways, cell proliferation, and apoptosis in a Barrett's adenocarcinoma cell line (SEG-1); and (2) the ability of acid to activate the MAPK pathways in vivo in patients with BE. Methods: SEG-1 cells were exposed to acidic media for 3 minutes, and the activities of 3 MAPKs (ERK, p38, and JNK) were determined. Proliferation was assessed using flow cytometry; cell growth and apoptosis were assessed using cell counts and an apoptosis ELISA assay. MAPK activation was studied in biopsy specimens taken from patients with BE before and after esophageal perfusion for 3 minutes with 0.1N HCI. Results: Acid-exposed SEG-1 cells exhibited a significant increase in proliferation and total cell numbers, and a significant decrease in apoptosis. These effects were preceded by a rapid increase in the activities of ERK and p38, and a delayed increase in JNK activity. PD 98059 abolished the acid-induced increase in GO/G1 and decrease in subGO phases of the cell cycle. Both SB 203580 and DN-JNK 1/2 inhibited the acid-induced progression from GO/G1 to G2/M. The acid-induced decrease in apoptosis was abolished by inhibition of either ERK or p38. In the patients, acid exposure significantly increased the activity of p38 in the metaplastic epithelium. Conclusions: Acid increases proliferation and survival, and decreases apoptosis in SEG-1 cells by activating the MAPK pathways. Acid also activates the MAPK pathways in BE in vivo. These findings suggest that acid might contribute to carcinogenesis in BE through activation of MAPK pathways.
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U2 - 10.1053/gast.2002.30993
DO - 10.1053/gast.2002.30993
M3 - Article
C2 - 11832445
AN - SCOPUS:0036161377
SN - 0016-5085
VL - 122
SP - 299
EP - 307
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -