19 1 2007 2 Chinese Bulletin of Life Sciences Vol. 19, No. 6 Feb., 2007 1004-0374(2007)01-0037-06 P4501B1 ( 750004) P450(cytochrome, CYP)1B1 P450 CYP1B1 CYP1B1 P4501B1 Q346.5 Q559.5 A Advances of cytochrome P4501B1 gene polymorphisms and their susceptibility to breast cancer LIU Chunlian, JIAO Haiyan * (Department of Medical Genetics and Cell Biology, Ningxia Medical College, Yinchuan 750004, China) Abstract: Cytochrome P450(CYP)1B1 is an important metabolic oxidase of P450 family. It distributes widely in extrahepatic tissues. The metabolism of CYP1B1 is regulated by exogenous carcinogens, estrogens and other factors. The CYP1B1 which function as the susceptible genes to breast cancer has many genetic polymorphisms. The polymorphisms, regulation mechanism and relation to breast cancer are reviewed in this paper. Key words: cytochrome P4501B1 polymorphisms breast cancer P450(cytochrome P450, CYP) CYP1B1 CYP1 (1990 ) (1991 ) CYP1B1 17α- CYP1B1 mrna CYP1B1 1 CYP1B1 CYP1B1 2p21 22 DNA 12 kb 3 2, mrna 5.2 kb 2 5' ( P450 1) 1 629 bp 543 [1] CYP1B1 CYP CYP1B1 23 CYP1B1*1 SNPs CYP1B1*2 CYP1B1*3 2006-04-26 2006-10-20 (NZ0535) (1981 ) (1965 ) *, E-mail: jiaohy@ nxmc.edu.cn
38 19 CYP1B1*4 CYP1B1*5 CYP1B1*6 CYP1B1*7 6 5 Arg48Gly(48C G) Ala119Ser(119G T) Leu432Val(432C G) Asn 453Ser(453A G) Ala443Gly(443C G) 51% 50% 53% 2% 7% CYP1B1*1~ CYP1B1*7 8% 37% 39% 2% 0.7% 6% 7% [2] CYP1B1*1 CYP1B1*2 CYP1B1*3 CYP1B1*4 CYP1B1*6 CYP1B1*7 14.3% 25.5% 38.8% 18.1% 0.4% 2.6% [3] ( 1) 3 453A G 443C G 432C G 432C G G/G G/C C/C 6.5% 23.0% 70.5% 14.5% 36.0% 49.5% 12.5% 34.8% 52.7% 2.6% 25.0% 72.4% CYP1B1 Bardiera [4] CYP1B1 COS-1 Ser453 CYP1B1*4 Asn453 5.0% CYP1B1*4 CYP1B1*1 CYP1B1*4 1.6h CYP1B1*1 4.8h CYP1B1*4 CYP1B1*4 CYP1B1*1 2 2.1 CYP1B1 (aryl hydrocarbon receptor, AhR) AhR (AhR nuclear translocator, ARNT) (xenobiotic responsive elements, XREs) CYP1B1 5' 834 853 CYP1B1 XREs Sp1( 824) CYP1B1 ( PAHs) AhR CYP1B1 AhR AhR Hsp90 Hsp90 AhR AhR DNA PAHs AhR Hsp90 ARNT -AhR/ ARNT XREs CYP1B1 XREs [5] CYP1B1 DNA DNA ( 2) Landi [6] 1976 1 CYP1B1 2 CYP1B1
1 P4501B1 39 TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) 121 CYP1B1 432C G 48C G 119G T 453A G 85.2% 49.6% 49.6% 28.7% RT-PCR 10 nmol L -1 TCDD CYP1B1 432C G mrna P450 TCDD Taylor [7] RNAi p300-2(src-2) CYP1B1 TCDD TCDD AhR CYP1B1 CYP1B1 MCF-7 CYP1B1 (TS) (B[a]P) Port [8] Western Northern-blotting CYP1B1 mrna CYP1B 1 mrna CYP1B1 mrna (P<0.05) PAH Spink [9] NaAsO 2 B[a]P T-47D CYP1A1 CYP1B1 B[a]P 2-4- 9 16 h 48h 10 µmol L -1 NaAsO 2 2-4- 86% 92% B[a]P CYP1A1 CYP1B1 mrnas NaAsO 2 I mrna NaAsO 2 B[a]P T-47D CYP1A1 CYP1B1 2.2 CYP1B1 RT-PCR ER MCF-7 10nmol L -1 E 2 12 h CYP1B1 mrna CYP1B1 152 +25 MCF-7 E 2 7 CYP1B1 63 49 (estrogen response element, ERE) ER ERE CYP1B1 E 2 CYP1B1 ER [10] E 2 E 2 /ER CYP1B1 ERE E 2 CYP1B1 4- (4-OH -E 2 ) DNA - E 2-3 4 E 2-3 4 DNA DNA ( 3) 17α- (17α-E 2 ) CYP1B1 2/4-OH-E 2 C-16α 16α-OH-E 2 CYP1B1 P450 Hanna [11] CYP1B1 4-OH-E 2 2-OH-E 2 16α-OH- 3 CYP1B1
40 19 E 2 CYP1B1 4-OH-E 2 2.4 3.4 CYP1B1 CYP1B1 Dawling [12] CYP1B1 E 2 E 2 E 2 2-MeOE 2 2-OH-3MeOE 2 2- OHE 2 4-MeOE 2 4-OHE 2 E 2 E 2 E 2 CYP1B1 2-OH-3MeOE 2 > 2-MeOE 2 >4-MeOE 2 E 2 CYP1B1 E 2 DNA 2.3 AhR-ER AhR- ER TCDD (1) TCDD CYP1B1 (2) AhR ER (3) AhR /ER ERE (4) TCDD ER (5) TCDD ER ER Takemoto [13] CYP1B1 AhR TCDD TCDD AhR CYP1B1 α (ERα) AhR Spink [14] MCF-7 RT-PCR 1nmol L -1 E 2 TCDD E 2 4, 2-OH- E 2 CYP1B1 CYP1A1 mrna (9 12 ) E 2 AhR ERα mrna AhRmRNA ARNT mrna MCF-7 AhR CYP1B1 CYP1A1 AhR Husbeck Powis [15] 1n mol L -1 E 2 TCDD 4-/2- CYP1B1/1A1mRNA E 2 AhR AH -1 (TRX-1) AhR/ARNT TCDD CYP1A1 CYP1B1 2.4 camp CYP1B1 P450 camp AhR [16] Tsuchiya [17] CYP1B1-1(SF-1) camp (CREB) SF-1 CYP1B1 SF-1a ( 1722) SF-1b ( 2474) SF-1 SF-1 K(PKA) SF-1a SF-1b pgl3 ( 2623/+25) PKA XRE CYP1B1 PKA 3 CYP1B1 Zheng [18] PCR-RFLP 432C G CC 53 46 (P 0.06) Leu /Leu Val/ Val 2~3 (95 CI 1.2 4.5) (OR 3.1 95% CI 1.0 9.1) (OR 1.9 95% CI 0.8 4.3) Kocabas [19] 432C G BMI OR 2.32 CI 1.26 4.25 BMI 24 kg m -2 Ahsan [20] CYP1B1*4 CYP1B1*5 280 1124 453G Rudqvist [21] CYP1B1 SNP CYP1B1*1 CYP1B1*2 CYP1B1*3 CYP1B1*4 8.7% 29.3% 44.4% 17.5%, CYP1B1 4, CYP1B1*3/*3 (OR 2.0 95%CI 1.1 3.5)
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