title: Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and -2 are differentially expressed in prostate cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Marcus
authors.initials: M
authors.lastname: Scharpf
authors.forename: Stefan Z
authors.initials: SZ
authors.lastname: Lutz
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.forename: David
authors.initials: D
authors.lastname: Schilling
authors.forename: Ursula
authors.initials: U
authors.lastname: Kühs
authors.forename: Valentina
authors.initials: V
authors.lastname: Gerber
authors.forename: Fausto
authors.initials: F
authors.lastname: Machicao
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism*; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin