Truncated 24kDa basic fibroblast growth factor
The invention relates to fragments of an amino acid sequence of mature, full length 24 kDa fibroblast growth factor- 2 or an analog thereof. The fragments have an activity that inhibits the migration of cultured cells as well as inhibiting angiogenesis, tumor growth, or any other processes that involve the migration of cells in vivo. This fragment does not stimulate the proliferation of cells which is in contrast to activity shown by the mature, full-length 24 kDa fibroblast growth factor- 2 . The present invention also relates to a DNA molecule encoding the fragment, an expression vector and a transformed host containing the DNA molecule, and a method of producing the protein by culturing the transformed host. Moreover, the present invention relates to a therapeutic composition the 24 kDa fibroblast growth factor fragment and a pharmaceutically acceptable carrier.
1. An isolated nucleic acid molecule comprising the nucleic acid molecule of SEQ ID NO: 5, wherein the nucleic acid molecule encodes for a polypeptide having at least one of anti-angiogenic, tumor suppressive or anti-migratory activity, but does not have stimulation of cell proliferation activity.
2. An isolated nucleic acid molecule 95% identical to SEQ ID NO: 5, wherein the nucleic acid molecule encodes a protein having at least one of anti-angiogenic, tumor suppressive or anti-migratory activity, but does not have stimulation of cell proliferation activity.
3. The isolated nucleic acid molecule of claim 1 , wherein said nucleic acid molecule is covalently linked to a detectable group.
4. The isolated nucleic acid molecule of claim 3 , wherein said detectable group is selected from the group consisting of radiolabel and fluorescent group.
5. The isolated nucleic acid molecule of claim 1 , wherein said nucleic acid molecule is operably linked to one or more expression control elements.
6. A vector comprising the nucleic acid of claim 1 .
7. A recombinant host cell, comprising the vector of claim 6 , whereby said cell is capable of expressing said nucleic acid.
8. The host cell of claim 7 , wherein said host is selected from the group consisting of prokaryotic and eukaryotic hosts.
9. A process for the production of a polypeptide having at least one of anti-angiogenic, tumor suppressive or anti-migratory activity, but does not have stimulation of cell proliferation activity, said process comprising:
a) growing under suitable nutrient conditions host cell transformed or transfected with the nucleic acid molecule of SEQ ID NO: 5; and
b) isolating the polypeptide products of the expression of the nucleic acid molecule.