Open AccessDefective Jak–Stat activation in renal cell carcinoma is associated with interferon‐α resistance
Author(s) -
Shang Donghao,
Liu Yuting,
Ito Noriyuki,
Kamoto Toshiyuki,
Ogawa Osamu
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00526.x
Subject(s) - cancer research , jak stat signaling pathway , renal cell carcinoma , stat1 , interferon , socs3 , signal transduction , tyrosine kinase 2 , cytokine , medicine , stat , biology , immunology , cancer , receptor , tyrosine kinase , stat3 , suppressor , microbiology and biotechnology , platelet derived growth factor receptor , growth factor
Chemotherapy is ineffective against metastatic renal cell carcinoma (RCC). Interferon (IFN)‐α has become the most common agent used in clinical therapy to overcome this malignant tumor, although a satisfactory response has not been achieved and the mechanism of resistance of RCC to IFN‐α remains unclear. The purpose of the present study was to evaluate the susceptibility of RCC cells to IFN‐α and clarify the mechanism of IFN‐α resistance in RCC. Six RCC cell lines and three types of IFN‐α were used, and the expression, activation and effects of transfection of possible proteins or factors reported to be involved in IFN‐α signaling were examined to clarify the mechanism of resistance. The results suggest that the resistance of RCC to IFN‐α is associated with the lack of Jak1, Tyk2 and Stat1 expression and defective Jak–Stat activation, but not with a lack of IFN‐α receptor, suppressors of cytokine signaling induction or other factors examined. Moreover, phosphorylation of Jak–Stat pathway components and reversion of IFN‐α resistance in RCC were observed upon transfection with Jak1, Tyk2 or Stat1 vector. These results suggest that restoring the expression of Jak or Stat1 might strikingly increase the susceptibility of RCC to IFN‐α and may be a new strategy for improving the response of RCC to IFN‐α treatment. The Jak–Stat pathway should therefore be an appropriate target for the treatment of RCC. ( Cancer Sci 2007; 98: 1259–1264)