Different subcellular localization of sulphotransferase 2B1b in human placenta and prostate

The human hydroxysteroid SULT (sulphotransferase) 2B1 subfamily consists of two isoforms, SULT2B1a and SULT2B1b. These two isoenzymes are transcribed from the same gene by alternative splicing of their first exons and share 94% amino acid sequence identity. The SULT2B1 isoforms are highly selective for the sulphation of 3β-hydroxysteroids. Immunoblot analysis of SULT2B1 expression in several human tissues indicates the presence of only SULT2B1b protein. Immunoreactive SULT2B1b protein was detected in human prostate, skin, placenta and lung tissue. SULT2B1b mRNA expression was detected in RNA isolated from term placenta, normal prostate, prostate carcinoma, benign prostate hyperplasia, LNCaP prostate cancer cells, breast cancer specimens and MCF-7 breast cancer cells. Immunohistochemical localization of SULT2B1b, in terms placental and prostate tissues, detected it in nuclei of placental syncytiotrophoblasts and cytoplasm of epithelial cells in prostate tissues. Immunoreactive and catalytically active SULT2B1b was identified in nuclei isolated from term human placenta. Also SULT2B1b was capable of translocating to nuclei in BeWo placental cells after stable transfection and differentiation. In contrast, immunohistochemical analysis of human prostate showed only cytosolic localization of SULT2B1b in the basal and luminal prostate epithelial cells. SULT2B1b was not detected in isolated nuclei from LNCaP prostate cancer cells but was present in the cytosolic fraction. Differential subcellular localization of SULT2B1b in prostate and placenta suggests that SULT2B1b may be differentially regulated and have different physiological functions in these two hormonally responsive human tissues.

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Effect of androgen signaling in stromal cells on growth of prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.297 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 297-297 ◽

Cited By ~ 3

Author(s):

Chun-Peng Liao ◽

Leng-Ying Chen ◽

Andrea Luethy ◽

Youngsoo Kim ◽

A. Robert MacLeod ◽

...

Keyword(s):

Prostate Cancer ◽

Epithelial Cells ◽

Cancer Cells ◽

Stromal Cells ◽

Culture System ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Epithelial Cancer ◽

Mesenchymal Transition

297 Background: Interactions between epithelial and stroma cells are important in the development of prostate cancer (PCa). Cancer-associated fibroblasts (CAFs) have been to support tumor progression, metastasis, and differentiation. Androgen receptor (AR) and related pathways are known to support the growth and survival of prostate epithelial cancer cells, the roles of AR-dependent processes in cancerous stroma are less clear. We sought to investigate if AR-dependent pathways present in CAF cells influence the growth and tumorogencity of epithelial cancer cells in relation to androgen-deprivation therapy in prostate cancer. Methods: Murine CAFs were isolated from a well-described PTEN-dependent cancer mouse model (Liao, et al Cancer Res, 2010. 70(18):7294). A co-culture system was developed based on multiple lines of murine CAFs grown along with human prostate cancer epithelial cells, and a murine-specific anti-sense oligonucleotide (ASO) against murine AR was used to specifically suppress AR expression in murine CAFs in this system. RT-PCR was used to investigate changes in gene expression. Results: Using this co-culture system, we found that murine CAFs promoted cell proliferation and colony formation in several human prostate cancer cell lines. Further, these processes were decreased by suppression of AR-expression in CAFs. Expression of genes related to tumorigenicity in epithelial cells were investigated. Markers associated with epithelial-mesenchymal transition (EMT, N-Cad) and “stemness” (OCT4, Sox2, Nanog) were increased in human prostate cancer cells grown with low-AR CAFs. Conclusions: Our data indicates that suppression of AR in CAFs results in down-regulation in the growth and tumorigenicity of prostate cancer cells through pathways related to EMT and “cell reprograming”. As such, development of therapies which inhibit the tumor-promoting pathways present in stromal cells may be one approach to improve the treatment of prostate cancer.

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Novel biomarker of specific castration-resistant prostate cancer (CRPC) by exploring the proteome analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.247 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 247-247 ◽

Cited By ~ 1

Author(s):

Hiroji Uemura ◽

Noriaki Arakawa ◽

Yusuke Itoh ◽

Takashi Kawahara ◽

Yasuhide Miyoshi ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Proteome Analysis ◽

Human Prostate ◽

Castration Resistant Prostate Cancer ◽

Prostate Cancer Cells ◽

Prostate Hyperplasia ◽

Castration Resistant ◽

Significant Difference ◽

Prostate Cancers

247 Background: It is well known that prostate specific antigen (PSA) level has no reliable correlation with pathological malignancy of prostate cancer and is not a predictor for the development of castration resistant prostate cancer (CRPC). The aim of this study is to explore novel biomarkers to predict the development of CRPC by using proteomics from secreted proteins from human prostate cancer cells. Methods: The proteins secreted from 6 prostate cancers in culture medium were analyzed and compared with 8 other cancer cells including renal and urothelial cancers using LTQ Orbitrap mass spectrometer. With the focus on high tissue specificity, the candidate biomarker proteins were then identified through analysis of gene expressions in proteins common to human prostate cancers by real time qPCR. Next, a system to measure the identified mouse monoclonal antibodies against the focused proteins was established. Finally, serum levels of these proteins from 33 patients with benign prostate hyperplasia (BPH), 31 with untreated prostate cancer (PCa) and 35 with CRPC, were measured. Results: The proteome analysis identified 12 candidates of secreted cell membrane proteins as new biomarkers. The proteome analysis indicated that not only matured GDF15, but pro-peptide as well as fragments (GDDP) are released from prostate cancer cells. Patients’ serum was analyzed for matured and pro-peptide GDF15 using ELISA and immunoprecipitation-MRM mass spectrometry. The results showed that the serum level of GDDP-1, one of the processing forms of GDDP, was significantly higher in CRPC than those in BPH and untreated PCa (P < 0.01). ROC analysis also showed that the AUC of GDDP-1(0.86) was higher than that of matured GDF15 (0.76). When the cutoff value of GDDP-1 was set at 4.0 ng/mL, there was a significant difference of overall survival (OS) in CRPC patients between those with more than 4.0 ng/mL compared to less than 4.0 ng/mL of GDDP-1, whereas there was no significant difference of OS measurable by PSA in CRPC patients. These data suggest that GDDP-1 may be a novel biomarker for CRPC. Conclusions: GDDP-1 shows potential as a novel biomarker for CRPC.

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