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Molecular and Cellular Biology, May 2000, p. 3266-3273, Vol. 20, No. 9
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Identification of a Series of Transforming Growth Factor beta -Responsive Genes by Retrovirus-Mediated Gene Trap Screening

Nobutake Akiyama,1 Yoshiyuki Matsuo,1 Heitetsu Sai,2 Makoto Noda,1,* and Shinae Kizaka-Kondoh1

Department of Molecular Oncology1 and Department of Radiology,2 Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan

Received 13 September 1999/Returned for modification 19 October 1999/Accepted 19 January 2000

Transforming growth factor beta  (TGF-beta ) plays important roles in the regulation of proliferation, differentiation, apoptosis, and carcinogenesis. To identify genes responsible for maintaining the phenotype induced by TGF-beta , we performed a retrovirus-mediated gene trap screening designed to isolate TGF-beta -responsive genes in human lung carcinoma cell line A549. After screening 249 trap lines, 21 were found to express the reporter beta -galactosidase gene in a TGF-beta -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-beta responsiveness of the endogenous genes was confirmed by RNA blot hybridization. In at least five cases, the TGF-beta -induced upregulation was found to be cycloheximide resistant, suggesting the roles of the genes in the TGF-beta -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-beta , such as epidermal growth factor receptor and beta 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]).

* Corresponding author. Mailing address: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. Phone: 81-75-751-4150. Fax: 81-75-751-4159. E-mail: mnoda{at}virus.kyoto-u.ac.jp.

Molecular and Cellular Biology, May 2000, p. 3266-3273, Vol. 20, No. 9
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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