Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth

被引:55
作者
Andrechek, ER
White, D
Muller, WJ
机构
[1] McGill Univ, Royal Victoria Hosp, Mol Oncol Grp, Montreal, PQ H3A 1A1, Canada
[2] McMaster Univ, Dept Biol, Inst Mol Biol & Biotechnol, Hamilton, ON L8S 4K1, Canada
[3] McMaster Univ, Dept Med Sci, Hamilton, ON L8S 4K1, Canada
基金
加拿大健康研究院;
关键词
ErbB2; mammary gland; mouse models; epithelium;
D O I
10.1038/sj.onc.1208230
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
The ErbB2 receptor tyrosine kinase has been implicated as a critical growth factor receptor in both normal development and cancer. Amplification and overexpression of this receptor is observed in 20-30% of all human breast cancers and is inversely correlated with patient survival. Studies with transgenic mice have established that elevated expression of erbB2 in mammary epithelium can directly induce mammary carcinomas. Although these studies confirmed a role for ErbB2 in breast cancer induction, the precise role of ErbB2 in normal mammary gland development remained to be elucidated due to the embryonic lethality associated with the null mutation. Here, we demonstrate that the mammary-specific ablation of erbB2 through Cre-mediated recombination leads to a striking ductal elongation defect. In addition to the observed elongation defect, we noted that branching in the adult mammary gland was also reduced. Despite these perturbations in virgin mammary gland morphogenesis, targeted disruption of erbB2 had little impact on the ability of these animals to lactate. Taken together, these observations indicate that erbB2 plays a critical role in the initial stages of mammary gland morphogenesis.
引用
收藏
页码:932 / 937
页数:6
相关论文
共 22 条
[1]   Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis [J].
Andrechek, ER ;
Hardy, WR ;
Siegel, PM ;
Rudnicki, MA ;
Cardiff, RD ;
Muller, WJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3444-3449
[2]  
Andrechek ER, 2003, CANCER RES, V63, P4920
[3]   ErbB2 is required for muscle spindle and myoblast cell survival [J].
Andrechek, ER ;
Hardy, WR ;
Girgis-Gabardo, AA ;
Perry, RLS ;
Butler, R ;
Graham, FL ;
Kahn, RC ;
Rudnicki, MA ;
Muller, WJ .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (13) :4714-4722
[4]   neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer [J].
Andrulis, IL ;
Bull, SB ;
Blackstein, ME ;
Sutherland, D ;
Mak, C ;
Sidlofsky, S ;
Pritzker, KPH ;
Hartwick, RW ;
Hanna, W ;
Lickley, L ;
Wilkinson, R ;
Qizilbash, A ;
Ambus, U ;
Lipa, M ;
Weizel, H ;
Katz, A ;
Baida, M ;
Mariz, S ;
Stoik, G ;
Dacamara, P ;
Strongitharm, D ;
Geddie, W ;
McCready, D .
JOURNAL OF CLINICAL ONCOLOGY, 1998, 16 (04) :1340-1349
[5]   STOCHASTIC APPEARANCE OF MAMMARY-TUMORS IN TRANSGENIC MICE CARRYING THE MMTV/C-NEU ONCOGENE [J].
BOUCHARD, L ;
LAMARRE, L ;
TREMBLAY, PJ ;
JOLICOEUR, P .
CELL, 1989, 57 (06) :931-936
[6]   REGULATION OF GENOMIC IMPRINTING BY GAMETIC AND EMBRYONIC PROCESSES [J].
CHAILLET, JR ;
BADER, DS ;
LEDER, P .
GENES & DEVELOPMENT, 1995, 9 (10) :1177-1187
[7]   A MUTATION IN THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN WAVED-2 MICE HAS A PROFOUND EFFECT ON RECEPTOR BIOCHEMISTRY THAT RESULTS IN IMPAIRED LACTATION [J].
FOWLER, KJ ;
WALKER, F ;
ALEXANDER, W ;
HIBBS, ML ;
NICE, EC ;
BOHMER, RM ;
MANN, GB ;
THUMWOOD, C ;
MAGLITTO, R ;
DANKS, JA ;
CHETTY, R ;
BURGESS, AW ;
DUNN, AR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (05) :1465-1469
[8]   The crystal structure of a truncated ErbB2 ectodomain reveals an active conformation, poised to interact with other ErbB receptors [J].
Garrett, TPJ ;
McKern, NM ;
Lou, MZ ;
Elleman, TC ;
Adams, TE ;
Lovrecz, GO ;
Kofler, M ;
Jorissen, RN ;
Nice, EC ;
Burgess, AW ;
Ward, CW .
MOLECULAR CELL, 2003, 11 (02) :495-505
[9]   Activated neu induces rapid tumor progression [J].
Guy, CT ;
Cardiff, RD ;
Muller, WJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (13) :7673-7678
[10]   Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation [J].
Jones, FE ;
Stern, DF .
ONCOGENE, 1999, 18 (23) :3481-3490