PURPOSE: Interferon-γ inhibits cancer cell proliferation and induces re-expression of different tumor suppressor genes.
As a candidate, HEPACAM is almost lost in bladder transitional cell carcinoma. To our knowledge whether interferon-γ inhibits BIU-87 proliferation and re-expresses HEPACAM mRNA is still unknown. Thus, we probed the mechanism and examined the correlations between interferon-γ in patient serum and HEPACAM in bladder transitional cell carcinoma.
MATERIALS AND METHODS: Using enzyme-linked immunosorbent assay we measured serum interferon-γ in 27 men and 6 women, and 15 volunteers. Disease was Ta-T1 in 12 patients, T2-T4 in 21, low grade in 25, high grade in 8, primary in 13 and recurrent in 20. A total of 33 cancer and 26 adjacent tissues were examined by immunohistochemistry to detect HEPACAM protein and ensure the position. Under interferon-γ stimulation we detected BIU-87 proliferation by MTT assay. Cell cycles were examined by flow cytometry. HEPACAM mRNA expression was determined by reverse transcription-polymerase chain reaction. Western blot was used to detect p21WAF1.
RESULTS: Interferon-γ was remarkably low in patients with bladder transitional cell carcinoma vs volunteers (p < 0.01). HEPACAM protein was highly expressed in adjacent tissue, mainly at the cytomembrane, but it was almost absent in bladder transitional cell carcinoma (p < 0.01). The interferon-γ decrease in the serum of patients with bladder transitional cell carcinoma and the low HEPACAM expression in tumors correlated linearly (r = 0.899, p < 0.01). In vitro interferon-γ inhibited BIU-87 proliferation (p < 0.01) and slightly re-expressed HEPACAM mRNA (p < 0.05). The cell cycle was arrested at G0/G1 and p21WAF1 was concurrently increased in response to interferon-γ (p < 0.01).
CONCLUSIONS: Results suggest an important connection between HEPACAM and interferon-γ, which may inhibit BIU-87 proliferation through HEPACAM re-expression and p21WAF1 up-regulation to arrest cells at the G0/G1 phase.
Written by:
Xu B, He Y, Wu X, Luo C, Liu A, Zhang J. Are you the author?
Department of Urology, First Affiliated Hospital and College of Laboratory Medicine, Key Laboratory of Medical Diagnostics of Education Ministry (CL), ChongQing Medical University, ChongQing, People's Republic of China.
Reference: J Urol. 2012 Oct;188(4):1346-53.
doi: 10.1016/j.juro.2012.06.005
PubMed Abstract
PMID: 22906662
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