PloS one, 2012-12, Vol.7 (12), p.e50953-e50953
2012
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- Autor(en) / Beteiligte
- Titel
- Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and -2 are differentially expressed in prostate cancer
- Ist Teil von
- PloS one, 2012-12, Vol.7 (12), p.e50953-e50953
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- In different cancers types, insulin receptor isoform composition or insulin receptor substrate (IRS) isoforms are different to healthy tissue. This may be a molecular link to increased cancer risk in diabetes and obesity. Since this is yet unclear for prostate cancer, we investigated IR isoform composition and IRS balance in prostate cancer compared to benign and tumor adjacent benign prostate tissue and brought this into relation to cell proliferation. We studied 23 benign prostate samples from radical cystectomy or benign prostatic hyperplasia surgery, 30 samples from benign tissue directly adjacent to prostate cancer foci and 35 cancer samples from different patients. RNA expression levels for insulin receptor isoforms A and B, IRS-1, IRS-2, and IGF-1 receptor were assessed by quantitative real-time RT-PCR. In addition, RNA- and protein expression of the cell cycle regulator p27(Kip1) was quantified by real-time RT-PCR and immunohistochemistry. Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates (p<0.05). IRS-1 to IRS-2 ratios were lower in malignant than in benign prostatic tissue (p<0.05). These altered ratios both in cancer and adjacent tissue were significantly associated with reduced p27(Kip1) content (p<0.02). Interestingly, IGF-1 receptor levels were significantly lower in patients with type 2 diabetes (p = 0.0019). We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0050953Titel-ID: cdi_plos_journals_1339597507
- Format
- –
- Schlagworte
- Aged, Benign, Biology, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Cancer, Cell cycle, Cell growth, Cell proliferation, Cyclin-dependent kinase inhibitor p27, Diabetes, Diabetes mellitus, Diabetes Mellitus, Type 2 - genetics, Diabetes Mellitus, Type 2 - metabolism, Diagnostic systems, Endocrinology, Gene expression, Gene Expression Regulation, Neoplastic, Health aspects, Health risks, Humans, Hyperplasia, Immunohistochemistry, Insulin, Insulin receptor substrate 1, Insulin Receptor Substrate Proteins - genetics, Insulin Receptor Substrate Proteins - metabolism, Insulin resistance, Insulin-like growth factor I, Insulin-like growth factors, Internal medicine, Isoforms, Kinases, Male, Malignancy, Medicine, Metabolic disorders, Metastasis, Middle Aged, Nephrology, Obesity, Patients, Polymerase chain reaction, Prostate - metabolism, Prostate cancer, Prostatectomy, Prostatic Hyperplasia - genetics, Prostatic Hyperplasia - metabolism, Prostatic Hyperplasia - surgery, Prostatic Neoplasms - genetics, Prostatic Neoplasms - metabolism, Prostatic Neoplasms - surgery, Proteins, Real time, Receptor, IGF Type 1 - genetics, Receptor, IGF Type 1 - metabolism, Receptor, Insulin - genetics, Receptor, Insulin - metabolism, Ribonucleic acid, RNA, Rodents, Signal transduction, Signaling, Studies, Substrates, Surgery, Type 2 diabetes, Urology