Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer. - Centre Oscar Lambret Accéder directement au contenu
Article Dans Une Revue PLoS Biology Année : 2011

Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.

Christopher A. Maxwell (1, 2) , Javier Benítez (3, 4) , Laia Gómez-Baldó (1, 2) , Ana Osorio (3, 4) , Núria Bonifaci (1, 2, 5) , Ricardo Fernández-Ramires (3, 4) , Sylvain V. Costes (6) , Elisabet Guinó (2, 5) , Helen Chen (7) , Gareth J. R. Evans (7) , Pooja Mohan (7) , Isabel Català (8) , Anna Petit (8) , Helena Aguilar (1) , Alberto Villanueva (1) , Alvaro Aytes (1) , Jordi Serra-Musach (1, 5) , Gad Rennert (9) , Flavio Lejbkowicz (9) , Paolo Peterlongo (10) , Siranoush Manoukian (11) , Bernard Peissel (11) , Carla B. Ripamonti (10, 11) , Bernardo Bonanni (12) , Alessandra Viel (13) , Anna Allavena (14) , Loris Bernard (15) , Paolo Radice (10) , Eitan Friedman (16, 17) , Bella Kaufman (16) , Yael Laitman (16) , Maya Dubrovsky (16) , Roni Milgrom (16) , Anna Jakubowska (18) , Cezary Cybulski (18) , Bohdan Gorski (18) , Katarzyna Jaworska (18) , Katarzyna Durda (18) , Grzegorz Sukiennicki (18) , Jan Lubiński (18) , Yin Yao Shugart (19) , Susan M. Domchek (20) , Richard Letrero (20) , Barbara L. Weber (20) , Frans B. L. Hogervorst (21) , Matti A. Rookus (22) , J Margriet Collee (23) , Peter Devilee (24) , Marjolijn J. Ligtenberg (25) , Rob B. van Der Luijt (26) , Cora M. Aalfs (27) , Quinten Waisfisz (28) , Juul Wijnen (29) , Cornelis E. P. van Roozendaal (30) , Douglas F. Easton (31) , Susan Peock (31) , Margaret Cook (31) , Clare Oliver (31) , Debra Frost (31) , Patricia Harrington (32) , D Gareth Evans (33) , Fiona Lalloo (33) , Rosalind Eeles (34) , Louise Izatt (35) , Carol Chu (36) , Diana Eccles (37) , Fiona Douglas (38) , Carole Brewer (39) , Heli Nevanlinna (40) , Tuomas Heikkinen (41) , Fergus J. Couch (42) , Noralane M. Lindor (43) , Xianshu Wang (42) , Andrew K. Godwin (44) , Maria A. Caligo (45) , Grazia Lombardi (45) , Niklas Loman (46) , Per Karlsson (47) , Hans Ehrencrona (48) , Anna Von Wachenfeldt (49) , Rosa Bjork Barkardottir (50) , Ute Hamann (51) , Muhammad U. Rashid (52, 53) , Adriana Lasa (54) , Trinidad Caldés (55) , Raquel Andrés (56) , Michael Schmitt (57) , Volker Assmann (58) , Kristen Stevens (59) , Kenneth Offit (60) , João Curado (61) , Hagen Tilgner (61) , Roderic Guigó (61) , Gemma Aiza (1) , Joan Brunet (62) , Joan Castellsagué (62) , Griselda Martrat (1) , Ander Urruticoechea (1) , Ignacio Blanco (62) , Laima Tihomirova (63) , David E. Goldgar (64) , Saundra Buys (65) , Esther M. John (66) , Alexander Miron (67, 68) , Melissa Southey (69) , Mary B. Daly (70) , Rita K. Schmutzler (71) , Barbara Wappenschmidt (71) , Alfons Meindl (72) , Norbert Arnold (73) , Helmut Deissler (74) , Raymonda Varon-Mateeva (75) , Christian Sutter (76) , Dieter Niederacher (77) , Evgeny Imyamitov (78) , Olga M. Sinilnikova (79, 80) , Dominique Stoppa-Lyonnet (81) , Sylvie Mazoyer (80) , Carole Verny-Pierre (80) , Laurent Castera (81) , Antoine de Pauw (81) , Yves-Jean Bignon (82) , Nancy Uhrhammer (82) , Jean-Philippe Peyrat (83) , Philippe Vennin (84) , Sandra Fert Ferrer (85) , Marie-Agnès Collonge-Rame (86) , Isabelle Mortemousque (87) , Amanda B. Spurdle (88) , Jonathan Beesley (88) , Xiaoqing Chen (88) , Sue Healey (88) , Mary Helen Barcellos-Hoff (6) , Marc Vidal (89, 90) , Stephen B. Gruber (91) , Conxi Lázaro (62) , Gabriel Capellá (62) , Lesley Mcguffog (31) , Katherine L. Nathanson (20) , Antonis C. Antoniou (31) , Georgia Chenevix-Trench (88) , Markus C. Fleisch (77) , Víctor Moreno (4, 5) , Miguel Angel Pujana (1, 4, 5)
1 Translational Research Laboratory
2 CIBERESP - Biomedical Research Centre Network for Epidemiology and Public Health
3 Human Genetics Group
4 Biomedical Research Centre Network for Rare Diseases
5 Biomarkers and Susceptibility Unit
6 Life Science Division [LBNL Berkeley]
7 Child and Family Research Institute
8 Department of Pathology
9 Department of Community Medicine and Epidemiology
10 Unit of Molecular Bases of Genetic Risk and Genetic Testing
11 Unit of Medical Genetics
12 Division of Cancer Prevention and Genetics
13 CRO - Centro di Riferimento Oncologico
14 Department of Genetics, Biology and Biochemistry
15 Department of Experimental Oncology
16 The Susanne Levy Gertner Oncogenetics Unit
17 Sackler Faculty of Medicine
18 Department of Genetics and Pathology
19 Unit of Statistical Genetics
20 Abramson Cancer Center
21 Family Cancer Clinic
22 Department of Epidemiology
23 Department of Clinical Genetics
24 Department of Genetic Epidemiology
25 Department of Human Genetics
26 Department of Clinical Molecular Genetics
27 Department of Clinical Genetics
28 Department of Clinical Genetics
29 Center for Human and Clinical Genetics
30 Department of Clinical Genetics
31 Centre for Cancer Genetic Epidemiology
32 Department of Oncology
33 Genetic Medicine
34 Oncogenetics Team
35 Clinical Genetics
36 Yorkshire Regional Genetics Service
37 Wessex Clinical Genetics Service
38 Institute of Human Genetics
39 Department of Clinical Genetics
40 Department of Obstetrics and Gynecology
41 Department of Obstetrics and Gynecology
42 Department of Laboratory Medicine and Pathology
43 Department of Medical Genetics
44 Department of Pathology and Laboratory Medicine
45 Section of Genetic Oncology
46 Department of Oncology
47 Department of Oncology
48 Department of Genetics and Pathology
49 Department of Oncology
50 Department of Pathology
51 Molecular Genetics of Breast Cancer
52 Molecular Genetics of Breast Cancer
53 Department of Basic Sciences
54 Servicio de Genética
55 Molecular Oncology Laboratory
56 Medical Oncology Division
57 Department of Internal Medicine III
58 Center for Experimental Medicine
59 Department of Epidemiology
60 Clinical Genetics Service
61 Bioinformatics and Genomics Group
62 Genetic Counseling and Hereditary Cancer Programme
63 Latvian Biomedical Research and Study Centre [Rīga]
64 Department of Dermatology
65 Department of Internal Medicine
66 Department of Epidemiology
67 Department of Cancer Biology
68 Department of Surgery
69 entre for Molecular, Environmental, Genetic and Analytic (MEGA) Epidemiology
70 Division of Population Science
71 Department of Gynaecology and Obstetrics
72 Department of Gynaecology and Obstetrics
73 Department of Gynaecology and Obstetrics
74 Department of Gynaecology and Obstetrics
75 Institute of Human Genetics
76 Institute of Human Genetics
77 Department of Gynaecology and Obstetrics
78 N. N. Petrov Institute of Oncology
79 Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents
80 GMSC - Génétique moléculaire, signalisation et cancer
81 Pathologie moléculaire des cancers
82 Département d'Oncogénétique
83 Laboratoire d'Oncologie Moléculaire Humaine
84 Consultation d'Oncogénétique
85 Laboratoire de Génétique Chromosomique
86 Département de Génétique et Reproduction
87 Service de génétique [Tours]
88 Queensland Institute of Medical Research
89 CCSB - Center for Cancer Systems Biology
90 Department of Genetics [Boston]
91 Department of Internal Medicine, Epidemiology, Human Genetics
Anna Jakubowska
Peter Devilee
D Gareth Evans
  • Fonction : Auteur
Fiona Lalloo
  • Fonction : Auteur
Rosalind Eeles
  • Fonction : Auteur
Louise Izatt
  • Fonction : Auteur
Trinidad Caldés
Antoine de Pauw

Résumé

Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.

Domaines

Cancer
Fichier principal
Vignette du fichier
journal.pbio.1001199.pdf (928.56 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

inserm-00706872 , version 1 (11-06-2012)

Identifiants

Citer

Christopher A. Maxwell, Javier Benítez, Laia Gómez-Baldó, Ana Osorio, Núria Bonifaci, et al.. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer.. PLoS Biology, 2011, 9 (11), pp.e1001199. ⟨10.1371/journal.pbio.1001199⟩. ⟨inserm-00706872⟩
1201 Consultations
379 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More