Skip Navigation


Carcinogenesis Advance Access originally published online on September 3, 2004
Carcinogenesis 2004 25(12):2293-2301; doi:10.1093/carcin/bgh272
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
25/12/2293    most recent
bgh272v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Gu, B.
Right arrow Articles by Sierra, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gu, B.
Right arrow Articles by Sierra, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Carcinogenesis vol.25 no.12 © Oxford University Press 2004; all rights reserved.

ARTICLE

Organ-selective chemoresistance in metastasis from human breast cancer cells: inhibition of apoptosis, genetic variability and microenvironment at the metastatic focus

Bin Gu1, Laura España1, Olga Méndez1, Angels Torregrosa2 and Angels Sierra1,3

1 Centre d'Oncologia Molecular, Institut de Recerca Oncológica, Hospital Duran i Reynals, Ciutat Sanitaria i Universitaria de Bellvitge, Barcelona, Spain and 2 Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain

3 To whom correspondence should be addressed Email: asierra{at}iro.es

We hypothesized that the development of the most resistant cells during metastasis is favored by anti-apoptotic proteins, leading to the acquisition of an adaptive phenotype crucial to drug resistance at the metastatic foci. In order to test it, we induced metastasis in nude mice, injecting orthotopicaly 435/Bcl-xL or 435/Neo cells, transfected previously with the luciferase gene to use it as a tumor marker, and treated them with a therapeutic dose of docetaxel. We monitored metastasis in mice by calculating tumor cell equivalents (TCEs) present in tissues. Between docetaxel-treated and non-treated 435/Bcl-xL.luc mice significant differences in the metastatic burden of lymph nodes (P = 0.02) and viscera (P = 0.02) were observed. However, treatment did not significantly decrease metastatic burden in bones (P = 0.19). Additionally, we analyzed the clonality of metastasis from lung, bone and lymph node by genomic DNA fingerprinting. Bcl-xL enhanced cell genetic instability in terms of gain and loss fractions (GF = 0.18 and LF = –0.21) when compared with the control 435/Neo (GF = 0.15 and LF = –0.14). Thus, genetic instability might be a molecular mechanism favored by Bcl-xL evolved in the selection process of breast cancer progression, which results in different genetic changes among metastases from lung, bone or lymph node, favoring organ-selective chemoresistance.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CarcinogenesisHome page
O. Mendez, B. Martin, R. Sanz, R. Aragues, V. Moreno, B. Oliva, V. Stresing, and A. Sierra
Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL
Carcinogenesis, June 1, 2006; 27(6): 1169 - 1179.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
H. Cortes-Funes, C. Gomez, R. Rosell, P. Valero, C. Garcia-Giron, A. Velasco, A. Izquierdo, P. Diz, C. Camps, D. Castellanos, et al.
Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients
Ann. Onc., July 1, 2005; 16(7): 1081 - 1086.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.