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Last Updated: April 26, 2024

Claims for Patent: 5,998,600

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Summary for Patent: 5,998,600

Title:	.beta.-catenin, TCF-4, and APC interact to prevent cancer
Abstract:	The APC tumor suppressor protein binds to .beta.-catenin, a protein recently shown to interact with Tcf/Lef transcription factors. Here, the gene encoding a Tcf family member that is expressed in colonic epithelium (hTcf-4) a was cloned and characterized. hTcf-4 transactivates transcription only when associated with .beta.-catenin. Nuclei of APC.sup.-/- colon carcinoma cells were found to contain a stable .beta.-catenin-hTCF-4 complex that was constitutively active, as measured by transcription of a Tcf reporter gene. Reintroduction of APC removed .beta.-catenin from hTcf4 and abrogated the transcriptional transactivation. Constitutive transcription of TCF target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium. It is also shown here that the products of mutant APC genes found in colorectal tumors are defective in regulating .beta.-catenin/Tcf-4 transcrpitional activation. Furthermore, colorectal tumors with intact APC genes were shown to contain subtle activating mutations of .beta.-catenin that altered functionally significant phosphorylation sites. These results indicate that regulation of .beta.-catenin is critical to APC\'s tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or .beta.-catenin.
Inventor(s):	Barker; Nick (Utrecht, NL), Clevers; Hans (Huis ter Heide, NL), Korinek; Vladimar (Prague, CZ)
Assignee:	Utrecht University (The Netherlands) N/A)
Application Number:	09/003,687
Patent Claims:	1. An intron-free DNA molecule encoding Tcf-4 protein as shown in SEQ ID NO:5 or 6. 2. The DNA molecule of claim 1 which has the nucleotide sequence of SEQ ID NO: 1 or 2.

Details for Patent 5,998,600

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Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986	⤷ Try a Trial	2017-03-20
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132		⤷ Try a Trial	2017-03-20
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132		⤷ Try a Trial	2017-03-20
>Applicant	>Tradename	>Biologic Ingredient	>Dosage Form	>BLA	>Approval Date	>Patent No.	>Expiredate

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