Loss of GRIM-19 Expression is Associated with Hyperactivation of STAT3-induced Gene Expression and T

来源 :BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会) | 被引量 : 0次 | 上传用户:wooool123
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  Cervical cancer is the most common malignant disease responsible for the deaths of a large number of women in the developing world.Although certain strains of HPV have been identified as the cause of this disease, events that lead to formation of malignant tumors are not fully clear.STAT3 is a major oncogenic transcription factor involved in the development and progression of a number of human tumors.However, the mechanisms that result in loss of control over STAT3 activity are not understood.GRIM-19 is a tumor-suppressive protein identified using a genetic technique in the interferon/retinoid induced cell death pathway.Here, we show that loss of GRIM-19 occurs in a number of primary human cervical cancers.Consequently, these tumors tend to express a high basal level of STAT3 and its downstream target genes.More importantly, we show that restoration of GRIM-19 levels reestablishes the control over STAT3-dependent gene expression and tumor growth in vivo.GRIM-19 suppressed the expression of tumor invasion-and angiogenesis-associated factors to limit tumor growth.This study identifies another major novel molecular pathway inactivated during the development human cervical cancer.
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