Cell cycle deregulation in liver lesions of rats with and without genetic predisposition to hepatocarcinogenesis

被引：70

作者：

Pascale, RM ^{[1
]}

Simile, MM ^{[1
]}

De Miglio, MR ^{[1
]}

Muroni, MR ^{[1
]}

Calvisi, DF ^{[1
]}

Asara, G ^{[1
]}

Casabona, D ^{[1
]}

Frau, M ^{[1
]}

Seddaiu, MA ^{[1
]}

Feo, F ^{[1
]}

机构：

[1] Univ Sassari, Dipartimento Sci Biomed, Sez Patol Sperimentale & Oncol, Div Expt Pathol & Oncol, I-07100 Sassari, Italy

来源：

HEPATOLOGY | 2002年 / 35卷 / 06期

关键词：

D O I：

10.1053/jhep.2002.33682

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Preneoplastic and neoplastic hepatocytes undergo c-Myc up-regulation and overgrowth in rats genetically susceptible to hepatocarcinogenesis, but not in resistant rats. Because c-Myc regulates the pRb-E2F pathway, we evaluated cell cycle gene expression in neoplastic nodules and hepatocellular carcinomas (HCCs), induced by initiation/selection (IS) protocols 40 and 70 weeks after diethylnitrosamine treatment, in susceptible Fisher 344 (F344) rats, and resistant Wistar and Brown Norway (BN) rats. No interstrain differences in gene expression occurred in normal liver. Overexpression of c-myc, Cyclins D1, E, and A, and E2F1 genes, at messenger RNA (mRNA) and protein levels, rise in Cyclin D1-CDK4, Cyclin E-CDK2, and E2F1-DP1 complexes, and pRb hyperphosphorylation occurred in nodules and HCCs of F344 rats. Expression of Cdk4, Cdk2, p16(INK4A), and p27(KIP1) did not change. In nodules and/or HCCs of Wistar and BN rats, low or no increases in c-myc, Cyclins D1, E, and A, and E2F1 expression, and Cyclin-CDKs complex formation were associated with p16(INK4A) overexpression and pRb hypophosphorylation. In conclusion, these results suggest deregulation of G1 and S phases in liver lesions of susceptible rats and block of G1-S transition in lesions of resistant strains, which explains their low progression capacity.

引用

页码：1341 / 1350

页数：10

共 51 条

[11]

De Miglio MR, 1999, MOL CARCINOGEN, V25, P21, DOI 10.1002/(SICI)1098-2744(199905)25:1<21::AID-MC3>3.3.CO

[12]

2-J

[13]

De Miglio MR, 1999, CANCER RES, V59, P4651

[14] Functional roles of E2F in cell cycle regulation [J].

Fan, JG ;

Bertino, JR .

ONCOGENE, 1997, 14 (10) :1191-1200

[15] Liver regeneration [J].

Fausto, N .

JOURNAL OF HEPATOLOGY, 2000, 32 :19-31

[16]

Feo F, 2000, CRIT REV ONCOGENESIS, V11, P19

[17]

FEO F, 1998, HUMAN POLYGENIC DIS, P189

[18]

GARCEA R, 1989, CANCER RES, V49, P1850

[19] Analysis of loss of heterozygosity in neoplastic nodules induced by diethylnitrosamine in the resistant BFF1 rat strain [J].

Gariboldi, M ;

Pascale, R ;

Manenti, G ;

De Miglio, MR ;

Calvisi, D ;

Carru, A ;

Dragani, TA ;

Feo, F .

CARCINOGENESIS, 1999, 20 (07) :1363-1368

[20]

Haddad R, 1997, CANCER RES, V57, P4615

← 1 2 3 4 5 6 →