The potential role of purine‐rich element binding protein (PUR) α as a novel treatment target for hormone‐refractory prostate cancer

Please cite this article as: Hunter, I., Hay, C.W., Esswein, B., Watt, K., McEwan, I.J., Tissue control of androgen action: The ups and downs of androgen receptor expression, Molecular and Cellular Endocrinology (2017), doi: 10.1016/j.mce.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Greatly reduced levels of pur-α are a feature of castrate resistant prostate cancer (CRPC) (Inoue et al 2008).…”

Section: Importance Of Regulatory Sequences In the Promoter And 5'utrmentioning

confidence: 99%

Tissue control of androgen action: The ups and downs of androgen receptor expression

Hunter

Hay

Esswein

et al. 2018

Molecular and Cellular Endocrinology

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show abstract

“…Multiple gels were run for each sample and at least three samples for each cell line were run at different times. The comparison of NMP patterns was done by image analysis software together with visual inspection (6,7). Protein spots significantly differentially expressed were excised for mass spectrometry analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Protein spots significantly differentially expressed were excised for mass spectrometry analysis. Mass spectrometry analysis was performed at the Mass Spectrometry/Proteomics Core Facility, The Johns Hopkins University School of Medicine (6,7,16).…”

Section: Methodsmentioning

confidence: 99%

“…One of the hallmarks of cancer cell adaption to the microenvironmental stresses, such as chemotherapeutics, heat and radiation, is alterations in the nuclear architecture (6)(7)(8). In concordance with these changes are alterations in nuclear matrix proteins (NMPs) which comprise the structural elements of the nucleus and likely act as a signature for tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Some specific NMP patterns associated with cancers, including bladder, prostate and colon cancers have been identified. Assessment of these NMP changes resulted in further elucidation of functional implications as well as the identification of biomarkers (6,7,(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Yin

Zhang

Zeng

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Abstract. Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel-resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel-resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxelresistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients.

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Down‐regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity

Zeng

Kulkarni

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J of Cellular Biochemistry

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The microenvironment of the cancer cell is pivotal to its phenotypic regulation. One of the central components of the microenvironment is temperature. An elevation in environmental temperature has been shown to increase the cancer cell's susceptibility to chemo- and radiation therapy. The goal of the studies described here was to identify some of the pathways that are modified by a mild increase in temperature in cancer cells. Using prostate cancer cells as a model system we found that in addition to the well described and anticipated up-regulation of the heat shock family of proteins, there is a significant down-regulation of certain members of the “cold shock” family of proteins such as, RNA binding motif protein 3 (RBM3) and cold inducible RNA binding protein (CIRBP). siRNA-mediated down-regulation of the cold shock protein (CSP) encoding mRNAs dramatically attenuates cell survival in the absence of any heat application. Furthermore, we also demonstrate that knocking down the CSPs can enhance the therapeutic response of prostate cancer cells to chemotherapy. Our findings suggest that down-regulating CSPs in cancer cells may “mimic” the stress response the cells experience when exposed to heat treatment rendering them more susceptible to therapy. Thus, the pharmacological modulation of RBM3 and CIRBP may represent novel therapeutic approaches for prostate cancer.

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The potential role of purine‐rich element binding protein (PUR) α as a novel treatment target for hormone‐refractory prostate cancer

Abstract: Further dissection of the role of PURalpha in cell growth regulation may reveal a novel target for HRPC.

Cited by 20 publications

References 28 publications

Tissue control of androgen action: The ups and downs of androgen receptor expression

Tissue control of androgen action: The ups and downs of androgen receptor expression

Downregulation of cytokeratin 18 is associated with paclitaxel-resistance and tumor aggressiveness in prostate cancer

Down‐regulating cold shock protein genes impairs cancer cell survival and enhances chemosensitivity

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