| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Physiology and Biophysics, University of Illinois and University of Illinois College of Medicine, Urbana, Illinois 61801 [L. D. R., B. S. K.], and Division of Hematology and Oncology, University of California Medical School, Los Angeles, California 90024 [D. K., D. J. S.]
Recent work has suggested that overexpression of the HER-2/neu protooncogene may play a role in the aggressive clinical behavior of some breast tumors. Since hormones are also known to change the proliferation rate and invasiveness of these cells, we have studied the effect of sex steroid hormones and antihormones on levels of the HER-2/neu mRNA and protein in human breast cancer cell lines using complementary DNA and antibody probes. In MCF-7 cells, which contain high levels of estrogen receptor and an estradiol (E2)-inducible progesterone receptor (PR), 1 nM E2 caused a rapid drop in HEr-2/neu mRNA (4.8 kilobases), to 40% of control values by 6 h, and a more gradual decrease in HER-2/neu protein, to 50% by 24 h. HER-2/neu protein and mRNA levels remained reduced throughout 1 week of E2 treatment. The effect of E2 was dose dependent, with the maximal effect seen with concentrations of 10–10 M E2 and above, and antiestrogen partly reversed the E2-induced decrease in HER-2/neu expression. These characteristics suggest that the observed modulation of HEr-2/neu is an estrogen receptor-mediated process. In contrast, progestins did not change HER-2/neu mRNA or protein levels in E2-primed MCF-7 cells that contain high levels of PR; in T47D cells, which contain low levels of ER and high levels of PR, addition of E2 or the progestin R5020 or the antiprogestin RU38,486 had no significant effect on HER-2/neu mRNA or protein levels over 6 days of treatment. These results indicate that estrogen but not progestin modulates HER-2/neu protooncogene expression in these breast cancer cell lines and suggest that aggressiveness associated with high levels of HER-2/neu mRNA and protein may be uncoupled from estrogen-stimulated proliferation in these cells.
1 Supported by NIH grants CA18119 and CA51482 and American Cancer Society grant PDT-370 (B. S. K) and by NIH grant CA36827 and American Cancer Society Faculty Research Award (D. J. S). Part of this work was presented at the 80th Annual Meeting of the American Association for Cancer Research, May 1989 (54).
2 To whom requests for reprints should be addressed, at Department of Physiology and Biophysics, University of Illinois, 524 Burrill Hall, 407 S. Goodwin Avenue, Urbana, IL 61801.
Received 7/20/89.
Revised 1/29/90.
This article has been cited by other articles:
|
|
 |
|
  A. U. Buzdar Role of biologic therapy and chemotherapy in hormone receptor- and HER2-positive breast cancer Ann. Onc., June 1, 2009; 20(6): 993 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Wilson and D. J. Slamon Evolving Understanding of Growth Regulation in Human Breast Cancer: Interactions of the Steroid and Peptide Growth Regulatory Pathways J Natl Cancer Inst, September 7, 2005; 97(17): 1238 - 1239. [Full Text] [PDF]
|
|
|
|
 |
|
 M. De Laurentiis, G. Arpino, E. Massarelli, A. Ruggiero, C. Carlomagno, F. Ciardiello, G. Tortora, D. D'Agostino, F. Caputo, G. Cancello, et al. A Meta-Analysis on the Interaction between HER-2 Expression and Response to Endocrine Treatment in Advanced Breast Cancer Clin. Cancer Res., July 1, 2005; 11(13): 4741 - 4748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Argiris, C.-X. Wang, S. G. Whalen, and M. P. DiGiovanna Synergistic Interactions between Tamoxifen and Trastuzumab (Herceptin) Clin. Cancer Res., February 15, 2004; 10(4): 1409 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jones Combining trastuzumab (Herceptin(R)) with hormonal therapy in breast cancer: what can be expected and why? Ann. Onc., December 1, 2003; 14(12): 1697 - 1704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Atalay, F. Cardoso, A. Awada, and M. J. Piccart Novel therapeutic strategies targeting the epidermal growth factor receptor (EGFR) family and its downstream effectors in breast cancer Ann. Onc., September 1, 2003; 14(9): 1346 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, S. M. Edgerton, S. D. Kosanke, T. L. Mason, K. M. Alvarez, N. Liu, R. T. Chatterton, B. Liu, Q. Wang, A. Kim, et al. Hormonal and Dietary Modulation of Mammary Carcinogenesis in Mouse Mammary Tumor Virus-c-erbB-2 Transgenic Mice Cancer Res., May 15, 2003; 63(10): 2425 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Lipton, S.M. Ali, K. Leitzel, L. Demers, H.A. Harvey, H.A. Chaudri-Ross, C. Brady, P. Wyld, and W. Carney Serum HER-2/neu and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen J. Clin. Oncol., May 15, 2003; 21(10): 1967 - 1972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. De Placido, M. De Laurentiis, C. Carlomagno, C. Gallo, F. Perrone, S. Pepe, A. Ruggiero, A. Marinelli, C. Pagliarulo, L. Panico, et al. Twenty-year Results of the Naples GUN Randomized Trial: Predictive Factors of Adjuvant Tamoxifen Efficacy in Early Breast Cancer Clin. Cancer Res., March 1, 2003; 9(3): 1039 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Rajendran, A. C. Nye, J. Frasor, R. D. Balsara, P. G. V. Martini, and B. S. Katzenellenbogen Regulation of Nuclear Receptor Transcriptional Activity by a Novel DEAD Box RNA Helicase (DP97) J. Biol. Chem., February 7, 2003; 278(7): 4628 - 4638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. DiGiovanna, P. Chu, T. L. Davison, C. L. Howe, D. Carter, E. B. Claus, and D. F. Stern Active Signaling by HER-2/neu in a Subpopulation of HER-2/neu-overexpressing Ductal Carcinoma in Situ: Clinicopathological Correlates Cancer Res., November 15, 2002; 62(22): 6667 - 6673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. I. Spiridon, M.-A. Ghetie, J. Uhr, R. Marches, J.-L. Li, G.-L. Shen, and E. S. Vitetta Targeting Multiple Her-2 Epitopes with Monoclonal Antibodies Results in Improved Antigrowth Activity of a Human Breast Cancer Cell Line in Vitro and in Vivo Clin. Cancer Res., June 1, 2002; 8(6): 1720 - 1730. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Lipton, S.M. Ali, K. Leitzel, L. Demers, V. Chinchilli, L. Engle, H. A. Harvey, C. Brady, C.M. Nalin, M. Dugan, et al. Elevated Serum HER-2/neu Level Predicts Decreased Response to Hormone Therapy in Metastatic Breast Cancer J. Clin. Oncol., March 15, 2002; 20(6): 1467 - 1472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Knoop, S. M. Bentzen, M. M. Nielsen, B. B. Rasmussen, and C. Rose Value of Epidermal Growth Factor Receptor, HER2, p53, and Steroid Receptors in Predicting the Efficacy of Tamoxifen in High-Risk Postmenopausal Breast Cancer Patients J. Clin. Oncol., July 15, 2001; 19(14): 3376 - 3384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamauchi, V. Stearns, and D. F. Hayes When Is a Tumor Marker Ready for Prime Time? A Case Study of c-erbB-2 as a Predictive Factor in Breast Cancer J. Clin. Oncol., April 15, 2001; 19(8): 2334 - 2356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Smith, A. A. Pollice, L.-P. Gu, K. A. Brown, S. G. Singh, L. E. Janocko, R. Johnson, T. Julian, D. Hyams, N. Wolmark, et al. Correlations Among p53, Her-2/neu, and ras Overexpression and Aneuploidy by Multiparameter Flow Cytometry in Human Breast Cancer: Evidence for a Common Phenotypic Evolutionary Pattern in Infiltrating Ductal Carcinomas Clin. Cancer Res., January 1, 2000; 6(1): 112 - 126. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Scoccia, Y. Mi Lee, C. Niederberger, and J. V. Ilekis Expression of the ErbB Family of Receptors in Ovarian Cancer Reproductive Sciences, May 1, 1998; 5(3): 161 - 165. [Abstract] [PDF]
|
|
| 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 |
