Cancer Research Meeting Calendar Telomeres
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
[Cancer Research 59, 5315-5322, October 1, 1999]
© 1999 American Association for Cancer Research
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tang, C. K.
Right arrow Articles by Lippman, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, C. K.
Right arrow Articles by Lippman, M. E.
[Cancer Research 59, 5315-5322, October 15, 1999]
© 1999 American Association for Cancer Research

Tumor Biology

Ribozyme-mediated Down-Regulation of ErbB-4 in Estrogen Receptor-positive Breast Cancer Cells Inhibits Proliferation Both in Vitro and in Vivo1

Careen K. Tang2, Xiao-Zheng Wu Concepcion, Melissa Milan, Xiaoqi Gong, Elizabeth Montgomery and Marc E. Lippman

Lombardi Cancer Center, Department of Biochemistry, Georgetown University Medical Center, Washington, DC 20007-2197

ErbB-4 is a recently discovered member of the class I receptor tyrosine kinase family (ErbB). Little is known about its expression and its importance in human malignancy. To delineate the biological function of ErbB-4 receptors in breast cancer, we used a hammerhead ribozyme strategy to achieve down-regulation of ErbB-4 receptors in various breast cancer cell lines. We observed that down-regulation of ErbB-4 in estrogen receptor-positive (ER+) human breast cancer cell lines (MCF-7 and T47D), which express relatively high levels of ErbB-4, significantly inhibited colony formation. No effects were observed in estrogen receptor-negative (ER-) MDA-MB-453 cells, which express low levels of endogenous ErbB4 and high levels of ErbB-2 and ErbB-3. This occurred despite the fact that fluorescence-activated cell sorter analysis of these latter cells revealed that the expression of the ErbB-4 receptor was completely abrogated by ribozyme treatment. Furthermore, down-regulation of ErbB-4 in T47D and MCF-7 cells significantly inhibited tumor formation in athymic nude mice (P < 0.03 and P < 0.001, respectively). In addition, NRG-stimulated phosphorylation of ErbB-4- and NRG-induced colony formation was significantly reduced in ribozyme-transfected T47D cells. These data provide the first evidence that elevation of ErbB-4 expression plays a role in the proliferation of some ER+ human breast cancer cell lines (T47D and MCF-7) that express high levels of ErbB-4.

We have also investigated the expression of ErbB-4 in human primary breast carcinoma specimens, using immunohistochemical staining with an anti-ErbB-4 monoclonal antibody. ErbB-4 expression was found in 60% of the 50 primary breast tumors examined, and high intense immunoreactivity of ErbB-4 was detected in 18% of these primary breast tumors. ErbB-4 receptor expression appeared to correlate with ER+ primary breast tumors. A similar correlation was also observed in the human breast cancer cell lines.

These results provide a better understanding of the biological significance of ErbB-4 receptor in breast cancer. Our data suggest that elevation of the ErbB-4 receptor plays a role in ER+ breast cancer cell proliferation. Moreover, ribozyme technology provides a useful tool to delineate the role of a particular gene product.




This article has been cited by other articles:


Home page
 Mol. Endocrinol.Home page
S.-M. Feng, C. I. Sartor, D. Hunter, H. Zhou, X. Yang, L. S. Caskey, R. Dy, R. S. Muraoka-Cook, and H. S. Earp III
The HER4 Cytoplasmic Domain, But Not Its C Terminus, Inhibits Mammary Cell Proliferation
Mol. Endocrinol., August 1, 2007; 21(8): 1861 - 1876.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Zhu, L. L. Sullivan, S. S. Nair, C. C. Williams, A. K. Pandey, L. Marrero, R. K. Vadlamudi, and F. E. Jones
Coregulation of Estrogen Receptor by ERBB4/HER4 Establishes a Growth-Promoting Autocrine Signal in Breast Tumor Cells
Cancer Res., August 15, 2006; 66(16): 7991 - 7998.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
J. A. Maatta, M. Sundvall, T. T. Junttila, L. Peri, V. J. O. Laine, J. Isola, M. Egeblad, and K. Elenius
Proteolytic Cleavage and Phosphorylation of a Tumor-associated ErbB4 Isoform Promote Ligand-independent Survival and Cancer Cell Growth
Mol. Biol. Cell, January 1, 2006; 17(1): 67 - 79.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. T. Junttila, M. Sundvall, M. Lundin, J. Lundin, M. Tanner, P. Harkonen, H. Joensuu, J. Isola, and K. Elenius
Cleavable ErbB4 Isoform in Estrogen Receptor-Regulated Growth of Breast Cancer Cells
Cancer Res., February 15, 2005; 65(4): 1384 - 1393.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. Barzon, M. Boscaro, and G. Palu
Endocrine Aspects of Cancer Gene Therapy
Endocr. Rev., February 1, 2004; 25(1): 1 - 44.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
R. Nahta, G. N. Hortobagyi, and F. J. Esteva
Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention
Oncologist, February 1, 2003; 8(1): 5 - 17.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
J.-L. Merlin, M. Barberi-Heyob, and N. Bachmann
In vitro comparative evaluation of trastuzumab (Herceptin(R)) combined with paclitaxel (Taxol(R)) or docetaxel (Taxotere(R)) in HER2-expressing human breast cancer cell lines
Ann. Onc., November 1, 2002; 13(11): 1743 - 1748.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. I. Sartor, H. Zhou, E. Kozlowska, K. Guttridge, E. Kawata, L. Caskey, J. Harrelson, N. Hynes, S. Ethier, B. Calvo, et al.
HER4 Mediates Ligand-Dependent Antiproliferative and Differentiation Responses in Human Breast Cancer Cells
Mol. Cell. Biol., July 1, 2001; 21(13): 4265 - 4275.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. M. R. Gilmour, K. G. Macleod, A. McCaig, W. J. Gullick, J. F. Smyth, and S. P. Langdon
Expression of erbB-4/HER-4 Growth Factor Receptor Isoforms in Ovarian Cancer
Cancer Res., March 1, 2001; 61(5): 2169 - 2176.
[Abstract] [Full Text]

Home page
 CROBMHome page
S. P. lyngstadaas
Synthetic Hammerhead Ribozymes as Tools in Gene Expression
Critical Reviews in Oral Biology & Medicine, January 1, 2001; 12(6): 469 - 478.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
V. Pawlowski, F. Revillion, M. Hebbar, L. Hornez, and J.-P. Peyrat
Prognostic Value of the Type I Growth Factor Receptors in a Large Series of Human Primary Breast Cancers Quantified with a Real-Time Reverse Transcription-Polymerase Chain Reaction Assay
Clin. Cancer Res., November 1, 2000; 6(11): 4217 - 4225.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
Q. L. Deveraux and J. C. Reed
IAP family proteins---suppressors of apoptosis
Genes & Dev., February 1, 1999; 13(3): 239 - 252.
[Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.