Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer
Eduardo J. Mascareno, Ivan Belashov, M. A.Q. Siddiqui, Fang Liu, Manya Dhar-Mascareno
Ernest Mario School of Pharmacy, Chemical Biology
Robert Wood Johnson Medical School (RWJMS), Center for Advanced Biotechnology and Medicine
BACKGROUND Androgen and TGF-β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines. RESULTS In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-β-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-β signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.
https://doi.org/10.1002/pros.21510
Published - Jun 15 2012
HEXIM1
SMAD phosphorylation
TGF-β
androgen receptor
mouse model
serine phosphorylation
10.1002/pros.21510
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Androgen Receptors Medicine & Life Sciences
Prostate Medicine & Life Sciences
Adenocarcinoma Medicine & Life Sciences
Normal Distribution Medicine & Life Sciences
Serine Medicine & Life Sciences
Mascareno, E. J., Belashov, I., Siddiqui, M. A. Q., Liu, F., & Dhar-Mascareno, M. (2012). Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer. Prostate, 72(9), 1035-1044. https://doi.org/10.1002/pros.21510
Mascareno, Eduardo J. ; Belashov, Ivan ; Siddiqui, M. A.Q. ; Liu, Fang ; Dhar-Mascareno, Manya. / Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer. In: Prostate. 2012 ; Vol. 72, No. 9. pp. 1035-1044.
@article{8739fefdb0f44afe86ee078954ab251c,
title = "Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer",
abstract = "BACKGROUND Androgen and TGF-β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines. RESULTS In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-β-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-β signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.",
keywords = "HEXIM1, RNA polymerase, SMAD phosphorylation, TGF-β, androgen receptor, mouse model, prostate cancer, serine phosphorylation",
author = "Mascareno, {Eduardo J.} and Ivan Belashov and Siddiqui, {M. A.Q.} and Fang Liu and Manya Dhar-Mascareno",
doi = "10.1002/pros.21510",
journal = "Prostate",
Mascareno, EJ, Belashov, I, Siddiqui, MAQ, Liu, F & Dhar-Mascareno, M 2012, 'Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer', Prostate, vol. 72, no. 9, pp. 1035-1044. https://doi.org/10.1002/pros.21510
Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer. / Mascareno, Eduardo J.; Belashov, Ivan; Siddiqui, M. A.Q.; Liu, Fang; Dhar-Mascareno, Manya.
In: Prostate, Vol. 72, No. 9, 15.06.2012, p. 1035-1044.
T1 - Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer
AU - Mascareno, Eduardo J.
AU - Belashov, Ivan
AU - Siddiqui, M. A.Q.
AU - Liu, Fang
AU - Dhar-Mascareno, Manya
N2 - BACKGROUND Androgen and TGF-β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines. RESULTS In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-β-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-β signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.
AB - BACKGROUND Androgen and TGF-β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines. RESULTS In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-β-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-β signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.
KW - HEXIM1
KW - RNA polymerase
KW - SMAD phosphorylation
KW - TGF-β
KW - androgen receptor
KW - mouse model
KW - prostate cancer
KW - serine phosphorylation
U2 - 10.1002/pros.21510
DO - 10.1002/pros.21510
JO - Prostate
JF - Prostate
Mascareno EJ, Belashov I, Siddiqui MAQ, Liu F, Dhar-Mascareno M. Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer. Prostate. 2012 Jun 15;72(9):1035-1044. https://doi.org/10.1002/pros.21510