ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo

Mathew Casimiro, Olga Rodriguez, Llana Pootrakul, Maral Aventian, Nadia Lushina, Caroline Cromelin, Georgina Ferzli, Kevin Johnson, Stanley Fricke, Fantahun Diba, Bhaskar Kallakury, Chioma Ohanyerenwa, Maxine Chen, Michael Ostrowski, Mien Chie Hung, Shafaat A. Rabbani, Ram Datar, Richard J Cote, Richard Pestell, Chris Albanese

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)4364-4372
Number of pages9
JournalCancer Research
Volume67
Issue number9
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

bcl-1 Genes
Cyclin D1
Prostate
Epithelial Cells
Prostatic Neoplasms
Epithelium
Cell Cycle
TYK2 Kinase
Neuregulin-1
Cell Line
cdc Genes
Neoplasms
Regulator Genes
In Vitro Techniques
Small Interfering RNA
Signal Transduction
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Carcinogenesis
Breast

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Casimiro, M., Rodriguez, O., Pootrakul, L., Aventian, M., Lushina, N., Cromelin, C., ... Albanese, C. (2007). ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. Cancer Research, 67(9), 4364-4372. https://doi.org/10.1158/0008-5472.CAN-06-1898

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 journalArticle

Casimiro, M, Rodriguez, O, Pootrakul, L, Aventian, M, Lushina, N, Cromelin, C, Ferzli, G, Johnson, K, Fricke, S, Diba, F, Kallakury, B, Ohanyerenwa, C, Chen, M, Ostrowski, M, Hung, MC, Rabbani, SA, Datar, R, Cote, RJ, Pestell, R & Albanese, C 2007, 'ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo', Cancer Research, vol. 67, no. 9, pp. 4364-4372. https://doi.org/10.1158/0008-5472.CAN-06-1898
Casimiro M, Rodriguez O, Pootrakul L, Aventian M, Lushina N, Cromelin C et al. ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. Cancer Research. 2007 May 1;67(9):4364-4372. https://doi.org/10.1158/0008-5472.CAN-06-1898
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. / ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo. In: Cancer Research. 2007 ; Vol. 67, No. 9. pp. 4364-4372.
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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.

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AU - Cote, Richard J

AU - Pestell, Richard

AU - Albanese, Chris

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