Dataset Information

Expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3 ⁷⁰⁵ in the epithelial cells of hormone-naive prostate cancer.

ABSTRACT:

Background

The signal transducer and activator of transcription 3 (STAT3) pathway is observed to be constitutively activated in several malignancies including prostate cancer (PCa). In the present study, we investigated the expression of total STAT3 (tSTAT3) and two forms of activated phosphorylated STAT3 (pSTAT3⁷²⁷ and pSTAT3⁷⁰⁵ ) in tissue microarrays (TMA) of two cohorts of localized hormone-naïve PCa patients and analyzed associations between the expression and disease outcome.

Methods

The expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3⁷⁰⁵ was scored in the nuclei and cytoplasm of prostatic gland epithelial cells in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö, Sweden (n = 300) and Dublin, Ireland (n = 99).

Results

The nuclear expression levels of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3⁷⁰⁵ in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Cytoplasmic tSTAT3 levels were also higher in benign glands. Patients with low pSTAT3⁷²⁷ and pSTAT3⁷⁰⁵ levels in the cancerous glands showed reduced times to biochemical recurrence, compared with those with higher levels. No significant trends in nuclear nor in cytoplasmic tSTAT3 were observed in relation to biochemical recurrence in the Malmö cohort. Higher cytoplasmic tSTAT3 was associated with reduced time to biochemical recurrence in the Dublin cohort. Adding the tSTAT3 and pSTAT3 expression data to Gleason score or pathological T stage did not improve their prognostic values.

Conclusions

Low pSTAT3⁷²⁷ and pSTAT3⁷⁰⁵ expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression. However, pSTAT3 and tSTAT3 expression did not improve the prognostic value of Gleason score or pathological T stage and may not be a good biomarker in the early hormone naïve stages of PCa.

SUBMITTER: Krzyzanowska A

PROVIDER: S-EPMC6766958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The treatment of advanced prostate cancer (PCa) remains a challenge. Identification of new molecular mechanisms that regulate PCa initiation and progression would provide targets for the development of new cancer treatments. The Foxm1 transcription factor is highly up-regulated in tumor cells, inflammatory cells, and cells of tumor microenvironment. However, its functions in different cell populations of PCa lesions are unknown. To determine the role of Foxm1 in tumor cells during PCa development, we generated two novel transgenic mouse models, one exhibiting Foxm1 gain-of-function and one exhibiting Foxm1 loss-of-function under control of the prostate epithelial-specific Probasin promoter. In the transgenic adenocarcinoma mouse prostate (TRAMP) model of PCa that uses SV40 large T antigen to induce PCa, loss of Foxm1 decreased tumor growth and metastasis. Decreased prostate tumorigenesis was associated with a decrease in tumor cell proliferation and the down-regulation of genes critical for cell proliferation and tumor metastasis, including Cdc25b, Cyclin B1, Plk-1, Lox, and Versican. In addition, tumor-associated angiogenesis was decreased, coinciding with reduced Vegf-A expression. The mRNA and protein levels of 11β-Hsd2, an enzyme playing an important role in tumor cell proliferation, were down-regulated in Foxm1-deficient PCa tumors in vivo and in Foxm1-depleted TRAMP C2 cells in vitro. Foxm1 bound to, and increased transcriptional activity of, the mouse 11β-Hsd2 promoter through the -892/-879 region, indicating that 11β-Hsd2 was a direct transcriptional target of Foxm1. Without TRAMP, overexpression of Foxm1 either alone or in combination with inhibition of a p19(ARF) tumor suppressor caused a robust epithelial hyperplasia, but was insufficient to induce progression from hyperplasia to PCa. Foxm1 expression in prostate epithelial cells is critical for prostate carcinogenesis, suggesting that inhibition of Foxm1 is a promising therapeutic approach for prostate cancer chemotherapy.

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Dataset Information

Expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3 ⁷⁰⁵ in the epithelial cells of hormone-naive prostate cancer.

Background

Methods

Results

Conclusions

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Expression of tSTAT3, pSTAT3727 , and pSTAT3 705 in the epithelial cells of hormone-naive prostate cancer.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Expression of tSTAT3, pSTAT3⁷²⁷ , and pSTAT3 ⁷⁰⁵ in the epithelial cells of hormone-naive prostate cancer.