Abstract
The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium.
| Original language | English |
|---|---|
| Pages (from-to) | 4364-4372 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. / Casimiro, Mathew; Rodriguez, Olga; Pootrakul, Llana; Aventian, Maral; Lushina, Nadia; Cromelin, Caroline; Ferzli, Georgina; Johnson, Kevin; Fricke, Stanley; Diba, Fantahun; Kallakury, Bhaskar; Ohanyerenwa, Chioma; Chen, Maxine; Ostrowski, Michael; Hung, Mien Chie; Rabbani, Shafaat A.; Datar, Ram; Cote, Richard J; Pestell, Richard; Albanese, Chris.
In: Cancer Research, Vol. 67, No. 9, 01.05.2007, p. 4364-4372.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo
AU - Casimiro, Mathew
AU - Rodriguez, Olga
AU - Pootrakul, Llana
AU - Aventian, Maral
AU - Lushina, Nadia
AU - Cromelin, Caroline
AU - Ferzli, Georgina
AU - Johnson, Kevin
AU - Fricke, Stanley
AU - Diba, Fantahun
AU - Kallakury, Bhaskar
AU - Ohanyerenwa, Chioma
AU - Chen, Maxine
AU - Ostrowski, Michael
AU - Hung, Mien Chie
AU - Rabbani, Shafaat A.
AU - Datar, Ram
AU - Cote, Richard J
AU - Pestell, Richard
AU - Albanese, Chris
PY - 2007/5/1
Y1 - 2007/5/1
N2 - The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium.
AB - The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium.
UR - http://www.scopus.com/inward/record.url?scp=34249301737&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249301737&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-1898
DO - 10.1158/0008-5472.CAN-06-1898
M3 - Article
VL - 67
SP - 4364
EP - 4372
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 9
ER -