Oncogenic activation of c-Abl tyrosine kinase in non-small cell lung cancer: FUS1 tumor suppressor down-regulates c-Abl tyrosine kinase

The FUS1 tumor suppressor gene (TSG) has been found to be deficient in many human non-small cell lung cancer (NSCLC) tissue samples and cell lines (1,2,3). Studies have shown potent anti-tumor activity of FUS1 in animal models where FUS1 was delivered through a liposomal vector (4) and the use of FUS1 as a therapeutic agent is currently being studied in clinical human trials (5). Currently, the mechanisms of FUS1 activity are being investigated and my studies have shown that c-Abl tyrosine kinase is inhibited by the FUS1 TSG.^ Considering that many NSCLC cell lines are FUS1 deficient, my studies further identified that FUS1 deficient NSCLC cells have an activated c-Abl tyrosine kinase. C-Abl is a known proto-oncogene and while c-Abl kinase is tightly regulated in normal cells, constitutively active Abl kinase is known to contribute to the oncogenic phenotype in some types of hematopoietic cancers. My studies show that the active c-Abl kinase contributes to the oncogenicity of NSCLC cells, particularly in tumors that are deficient in FUS1, and that c-Abl may prove to be a viable target in NSCLC therapy.^ Current studies have shown that growth factor receptors play a role in NSCLC. Over-expression of the epidermal growth factor receptor (EGFR) plays a significant role in aggressiveness of NSCLC. Current late stage treatments include EFGR tyrosine kinase inhibitors or EGFR antibodies. Platelet-derived growth factor receptor (PDGFR) also has been shown to play a role in NSCLC. Of note, both growth factor receptors are known upstream activators of c-Abl kinase. My studies indicate that growth factor receptor simulation along deficiency in FUS1 expression contributes to the activation of c-Abl kinase in NSCLC cells. ^

Editorial: Take Me Home, Down Country Roads

Those of us committed to the tenets of Family Preservation must advocate for increased awareness and attention to the needs of children and their families in rural America. "Country roads" and the rural spaces they traverse have been eulogized by many poets and song writers as ideal places to live. But they may not be ideal for everyone. The past few months, it has become all too evident that rural America is not immune to acts of extreme violence by troubled children. Even though almost 1/3 of American youth live in rural areas, they have been "virtually ignored by mental health service planners and providers"(Cutrona, Halvorson, & Russell, 1996, p. 217). Mental health risk factors such as poverty, parental alcohol abuse, and family instability are on the rise in rural areas, and there has been an increase in suicide attempts, family violence, depression, and alcohol abuse (Cutrona, Halvorson, & Russell, 1996; Petti & Leviton, 1986; National Mental Health Association, 1988). Native Americans are especially concerned about the increases in child abuse and neglect, depression, substance abuse, and suicide in their communities.

Hunting Down Dead People: Genealogy Resources in the Iowa State University Library

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