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Researchers find important 'target' playing role in tobacco-related lung cancers
Date:2/9/2012

TAMPA, Fla. (Feb. 9, 2012) Researchers at Moffitt Cancer Center in Tampa, Fla., have discovered that the immune response regulator IKBKE (serine/threonine kinase) plays two roles in tobacco-related non-small cell lung cancers. Tobacco carcinogens induce IKBKE and, in turn, IKBKE induces chemotherapy resistance.

The study was published in a recent issue of Oconogene.

"IKBKE is a newly identified oconogene, a gene linked to cancer," said study lead author Jin Q. Cheng, Ph.D., M.D., who studies genetic alterations and their molecular mechanisms in cancer. "In our study, we demonstrated that IKBKE is a STAT 3 target gene and is induced by tobacco. STAT3 is a signaling and transcription gene that is activated in various types of cancer and is required for cell transformation."

As a "transcription factor" STAT3 plays a key role in many cellular processes, such as cell growth and programmed cell death, or "apoptosis."

"It has been well documented that STAT3 is activated by growth factors and environmental carcinogenesis, such as nicotine," said Cheng. "STAT3 directly binds to the IKBKE promoter and induces IKBKE transcription."

Tobacco smoke is the strongest documented tumor initiator and promoter in lung cancer. The underlying molecular mechanism is still largely unknown.

"IKBKE is induced by tobacco carcinogens and mediates tobacco action in promoting lung cancer cell survival," said Cheng. "Armed with this knowledge, interventions targeting the IKBKE pathway could be developed."

Cheng and his colleagues found that when STAT3 induces IKBKE expression, IKBKE's expression induces chemotherapy resistance. Conversely, "knocking down" IKBKE sensitizes cells to chemotherapy, suggesting that there is a therapeutic role for targeting IKBKE.

While IKBKE has been found to be "over expressed" in ovarian, breast and prostate cancers, in this study IKBKE has for the first time been associated with n
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Contact: Ferdie De Vega
Ferdinand.DeVega@moffitt.org
813-745-7858
H. Lee Moffitt Cancer Center & Research Institute
Source:Eurekalert

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