Influence of retinoic acid on adhesion complexes in human hepatoma cells: A clue to its antiproliferative effects

被引:16
作者
Ara, C [1 ]
Devirgiliis, LC [1 ]
Massimi, M [1 ]
机构
[1] Univ Aquila, Dipartimento Biol Base & Appl, I-67010 Coppito, Italy
关键词
beta-catenin; E-cadherin; HepG2; occludin; ZO-1;
D O I
10.1080/15419060490471757
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Retinoic acid exerts antiproliferative and differentiative effects in normal and transformed in vitro hepatocytes. In order to verify whether these effects are related to a modulation of adhesion molecules, we used Western blot analysis and immunofluorescence microscopy to investigate the E-cadherin/beta-catenin complex, the main system of adherens junctions, and the occludin/ZO-1 complex present in the tight junctions in HepG2 cells cultured in the presence or absence of retinoic acid. Results showed that retinoic acid treatment increases the amount of beta-catenin bound to E-cadherin by decreasing its tyrosine-phosphorylation level. Similar results were obtained with the tight junction system, in which the amount of occludin/ZO-1 complex is increased by a similar mechanism that reduced the level of ZO-1 phosphorylation on tyrosine. Immunofluorescence images also confirm these results, showing the localization on the cell surface of both adhesion complexes. Their insertion into the plasma membrane could be suggestive of an optimal reassembly and function of adherens and tight junctions in hepatoma cells, indicating that retinoic acid, besides inhibiting cell proliferation, improves cell-cell adhesion, sustaining or inducing the expression of a more differentiated phenotype.
引用
收藏
页码:13 / +
页数:12
相关论文
共 55 条
[1]   Retinoic acid modulates the cell-cycle in fetal rat hepatocytes and HepG2 cells by regulating cyclin-cdk activities [J].
Alisi, A ;
Leoni, S ;
Piacentani, A ;
Devirgiliis, LC .
LIVER INTERNATIONAL, 2003, 23 (03) :179-186
[2]  
ANDERSON JM, 1995, AM J PHYSIOL, V269, pG476
[3]  
Ando-Akatsuka Y, 1999, J CELL PHYSIOL, V179, P115, DOI 10.1002/(SICI)1097-4652(199905)179:2<115::AID-JCP1>3.0.CO
[4]  
2-T
[5]  
Aplin AE, 1998, PHARMACOL REV, V50, P197
[6]   Retinoic acid modulates gap junctional intercellular communication in hepatocytes and hepatoma cells [J].
Ara, C ;
Massimi, M ;
Devirgiliis, LC .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2002, 59 (10) :1758-1765
[7]   LOSS OF EPITHELIAL DIFFERENTIATION AND GAIN OF INVASIVENESS CORRELATES WITH TYROSINE PHOSPHORYLATION OF THE E-CADHERIN BETA-CATENIN COMPLEX IN CELLS TRANSFORMED WITH A TEMPERATURE-SENSITIVE V-SRC GENE [J].
BEHRENS, J ;
VAKAET, L ;
FRIIS, R ;
WINTERHAGER, E ;
VANROY, F ;
MAREEL, MM ;
BIRCHMEIER, W .
JOURNAL OF CELL BIOLOGY, 1993, 120 (03) :757-766
[8]   Cytoskeletal and adhesion proteins as tumor suppressors [J].
BenZeev, A .
CURRENT OPINION IN CELL BIOLOGY, 1997, 9 (01) :99-108
[9]   CADHERIN EXPRESSION IN CARCINOMAS - ROLE IN THE FORMATION OF CELL-JUNCTIONS AND THE PREVENTION OF INVASIVENESS [J].
BIRCHMEIER, W ;
BEHRENS, J .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1994, 1198 (01) :11-26
[10]   TCF/LEF factors earn their wings [J].
Clevers, H ;
Van de Wetering, M .
TRENDS IN GENETICS, 1997, 13 (12) :485-489