Skip Navigation


Annals of Oncology Advance Access originally published online on January 8, 2009
Annals of Oncology 2009 20(3):441-448; doi:10.1093/annonc/mdn651
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
20/3/441    most recent
mdn651v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
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 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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Liu, T.
Right arrow Articles by Zhang, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, T.
Right arrow Articles by Zhang, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

Increased {gamma}-tubulin expression and P16INK4A promoter methylation occur together in preinvasive lesions and carcinomas of the breast

T. Liu, Y. Niu*, Y. Yu, Y. Liu and F. Zhang

Breast Cancer Research Key Laboratory of National Education Ministry, Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China

* Correspondence to: Prof. Y. Niu, Breast Cancer Research Key Laboratory of National Education Ministry, Cancer Institute and Hospital, Tianjin Medical University, Huan Hu Xi Road, Ti Yuan Bei, He Xi District, Tianjin 300060, China. Tel: +86-22-23340123-5221; Fax: +86-22-23359337; E-mail: yunniu2000{at}yahoo.com.cn

Background: Loss of p16INK4A due to promoter hypermethylation is correlated with the ability to acquire centrosomal abnormalities in variant human mammary epithelial cells. {gamma}-Tubulin is a highly conserved component of centrosome in most animal cells and {gamma}-tubulin protein overexpression could lead to centrosome aberration.

Materials and methods: A large series of breast premalignant lesions and carcinoma was analyzed. Real-time quantitative PCR and immunohistochemistry were carried out to measure {gamma}-tubulin copy numbers and protein expression. MethyLight and immunohistochemistry were carried out to determine p16INK4A methylation and protein expression.

Results: {gamma}-Tubulin protein expression was concordant with gene amplification; both of them were found to increase with atypical ductal hyperplasia–carcinoma sequence. The median value and positive rate of p16INK4a methylation increased while protein expression displayed a decreasing trend. P16INK4a methylation showed a firm association with {gamma}-tubulin gene amplification.

Conclusion: {gamma}-Tubulin gene amplification and the concomitant protein overexpression present not only in invasive carcinoma but also in a significant fraction of atypical hyperplasia and in situ carcinomas. P16INK4a methylation and {gamma}-tubulin gene amplification had a synergistic effect on tumor progression. The synergism might arise as a result of the combined influence that p16INK4a and {gamma}-tubulin have on the G1–S cell cycle checkpoints and centrosome.

Key words: ADH–carcinoma sequence, immunohistochemistry, p16INK4A, real-time quantitative PCR, {gamma}-tubulin

Received for publication July 31, 2008. Accepted for publication September 1, 2008.


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




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.