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Transforming growth factor ␤ (TGF-␤) plays important roles in the regulation of proliferation, differentiation, apoptosis, and carcinogenesis. To identify genes responsible for maintaining the phenotype induced by TGF-␤, we performed a retrovirus-mediated gene trap screening designed to isolate TGF-␤-responsive genes in human lung carcinoma cell line A549. After screening 249 trap lines, 21 were found to express the reporter ␤-galactosidase gene in a TGF-␤-responsive manner. Interestingly, in large proportions of these trap lines, the reporter gene was responsive also to phorbol ester and was suppressed by gamma interferon. Fragments of all these trapped genes were recovered by 5-and 3-rapid amplification of cDNA ends (RACE), and in 15 out of 21 cases (71%), the TGF-␤ responsiveness of the endogenous genes was confirmed by RNA blot hybridization. In at least five cases, the TGF-␤-induced upregulation was found to be cycloheximide resistant, suggesting the roles of the genes in the TGF-␤-induced primary responses. Sequence analyses revealed that 43% (9 of 21) of the trapped genes were novel and that the remainder included genes previously reported to be upregulated by TGF-␤, such as epidermal growth factor receptor and ␤1 integrin, documenting the validity of this approach. Other known genes include the ones encoding the proteins associated with cell proliferation (ribosomal proteins S15a, hNRP/NAP-1, and lipocortin II), focal adhesions (paxillin), and transcriptional regulation (thyroid hormone receptor activator molecule 1 [TRAM-1]).

Esophageal stenting in previously irradiated patients is known to cause more severe complications than those in patients who were not irradiated. But there are few reports regarding the results of stent placement before radiation therapy. Three patients with stage T4 esophageal cancer with direct invasion to the trachea and/or aorta underwent radiation therapy after stent placement. Two of the three patients had received systemic chemotherapy before radiation therapy. Fifty-one to 66 Gy of radiation therapy was administrated 15 to 66 days after the stent placement. The initial response to radiation therapy was no change (NC) or progressive disease (PD). All patients died of bleeding or pneumonia caused by perforation at the site of the stents 17 to 79 days after the radiation therapy. It is strongly suggested that even in patients with locally advanced esophageal cancer with severe dysphagia, radiation therapy should precede stent placement, because the consequences of radiation therapy after stent placement are devastating, and radiation therapy alone can, potentially, resolve the symptoms.