TY - JOUR
T1 - Comparative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on MCF-7, RL95-2, and LNCaP cells
T2 - Role of target steroid hormones in cellular responsiveness to CYP1A1 induction
AU - Jana, Nihar Ranjan
AU - Sarkar, Shubhashishi
AU - Ishizuka, Mayumi
AU - Yonemoto, Junzo
AU - Tohyama, Chiharu
AU - Sone, Hideko
N1 - Funding Information:
We thank Professor P. Chambon (IGBMC, INSERM, France), Dr. C. M. Klinge (University of Louisville, KY),and the late Dr. K. Ume-sono (Institute for Virus Research, Kyoto University, Japan) for providing HEO and the pGL3-3 (EREc38)-LUC and MMTV-LUC plasmids, respectively. This work was supported in part by grants from the Science and Technology Agency to N.R.J. and S.S.
PY - 2000
Y1 - 2000
N2 - A study was conducted to investigate whether target hormones affect 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible gene expression, using as an experimental model system three human cancer cell lines, breast (MCF-7), uterine (RL95-2), and prostate (LNCaP). Exposure to TCDD induced the CYP1A1 gene in all three cell lines. MCF-7 and RL95-2 cells showed more than 15- and 10-fold induction of EROD (7-ethoxyresorufin O-deethylase) activity, respectively, compared with the less responsive LNCaP cells. Surprisingly, however, TCDD-induced reporter gene activity driven by a single XRE element was similar in RL95-2 and LNCaP cells. The steady-state levels of expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) were similar in all three cell lines. Expression of the CYP1B1 and PAI-2 genes was induced by TCDD in MCF-7 and RL95-2, but not in LNCaP, cells. Transient coexpression of estradiol receptor-α (ER-α) with a TCDD-responsive reporter plasmid and subsequent TCDD treatment increased responsiveness to TCDD in RL95-2 and LNCaP cells. Treatment with AZA-C, a DNA methyltransferase inhibitor, enhanced responsiveness to TCDD, in terms of EROD activity in LNCaP cells, but not in MCF-7 and RL95-2 cells, suggesting that DNA methylation in the CpG dinucleotide within the XRE core sequence is another factor involved in silencing of CYP1A1 in LNCaP cells. TCDD markedly inhibited E2- or testosterone-induced reporter gene activities in all three cell lines. Conversely, these target hormones inhibited TCDD-induced EROD activity in the three cell lines. These findings suggest that TCDD and the target steroid hormones negatively regulate each other's activity.
AB - A study was conducted to investigate whether target hormones affect 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible gene expression, using as an experimental model system three human cancer cell lines, breast (MCF-7), uterine (RL95-2), and prostate (LNCaP). Exposure to TCDD induced the CYP1A1 gene in all three cell lines. MCF-7 and RL95-2 cells showed more than 15- and 10-fold induction of EROD (7-ethoxyresorufin O-deethylase) activity, respectively, compared with the less responsive LNCaP cells. Surprisingly, however, TCDD-induced reporter gene activity driven by a single XRE element was similar in RL95-2 and LNCaP cells. The steady-state levels of expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) were similar in all three cell lines. Expression of the CYP1B1 and PAI-2 genes was induced by TCDD in MCF-7 and RL95-2, but not in LNCaP, cells. Transient coexpression of estradiol receptor-α (ER-α) with a TCDD-responsive reporter plasmid and subsequent TCDD treatment increased responsiveness to TCDD in RL95-2 and LNCaP cells. Treatment with AZA-C, a DNA methyltransferase inhibitor, enhanced responsiveness to TCDD, in terms of EROD activity in LNCaP cells, but not in MCF-7 and RL95-2 cells, suggesting that DNA methylation in the CpG dinucleotide within the XRE core sequence is another factor involved in silencing of CYP1A1 in LNCaP cells. TCDD markedly inhibited E2- or testosterone-induced reporter gene activities in all three cell lines. Conversely, these target hormones inhibited TCDD-induced EROD activity in the three cell lines. These findings suggest that TCDD and the target steroid hormones negatively regulate each other's activity.
KW - 2,3,7,8-tetrachlorodibenzo-p-dioxin
KW - AhR
KW - CYP1A1
KW - ER
KW - Human cells
KW - Steroid hormone
UR - http://www.scopus.com/inward/record.url?scp=0034451228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034451228&partnerID=8YFLogxK
U2 - 10.1006/mcbr.2001.0275
DO - 10.1006/mcbr.2001.0275
M3 - Article
C2 - 11281733
AN - SCOPUS:0034451228
VL - 4
SP - 174
EP - 180
JO - Molecular Cell Biology Research Communications
JF - Molecular Cell Biology Research Communications
SN - 1522-4724
IS - 3
ER -