Promotion of cell proliferation by use of transforming growth factor beta (TGF-β)

Claim 1

A method for promoting cell proliferation in mammals which comprises applying to a mammal in need of such treatment an effective amount of beta-transforming growth factor (TGF-β) having the following characteristics; (a) does not compete with epidermal growth factor (EGF) for receptor binding; (b) induces dose dependent formation of large colonies having a size of greater than 3,100 μm 2 of NRK 49F cells in a soft agar assay when activated by EGF or transforming growth factor-alpha (TGF-α) and (c) if not activated by EGF or transforming growth factor-alpha, does not induce NRK cells to form said large colonies in soft agar.

Claim 2

A method for promoting cell proliferation in mammals which comprises applying to a mammal in need of such treatment an effective amount of beta-transforming growth factor (TGF-β) having the following characteristics; (a) does not compete with epidermal growth factor (EGF) for receptor binding; (b) induces dose dependent formation of large colonies having a size of greater than 3,100 μm 2 of NRK 49F cells in a soft agar assay when activated by EGF or transforming growth factor-alpha (TGF-α) and (c) if not activated by EGF or transforming growth factor-alpha, does not induce NRK cells to form said large colonies in soft agar.

Claim 5

A method for promoting cell proliferation in mammals which comprises applying to a mammal in need of such treatment an effective amount of a composition comprising: an effective cell proliferation enhancing amount of isolated and substantially homogeneous beta transforming growth factor (TGF-β) having the following characteristics: (a) acid stable; (b) an apparent molecular weight of about 25,000 to 26,000 daltons in the absence of a reducing agent as measured by SDS-PAGE; (c) an apparent molecular weight of about 12,500 daltons under reducing conditions as measured by SDS-PAGE; (d) does not compete with epidermal growth factor for receptor binding; (e) induces dose-dependent formation of large colonies having a size of greater than 3,100 μm 2 of NRK 49F cells in a soft agar assay when activated by epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-α); and being purified to the extent that (1) it does not itself induce NRK cells to form said large colonies in soft agar and (2) a single band with an apparent molecular weight of about 12,500 daltons is shown on SDS-PAGE under reducing conditions and a single band with an apparent molecular weight of about 25,000 is shown under non-reducing conditions; and a pharmaceutically acceptable carrier therefor.

Claim 6

A method for promoting cell proliferation in mammals which comprises applying to a mammal in need of such treatment an effective amount of a composition comprising: an effective cell proliferation enhancing amount of isolated and substantially homogeneous beta transforming growth factor (TGF-β) having the following characteristics: (a) acid stable; (b) an apparent molecular weight of about 25,000 to 26,000 daltons in the absence of a reducing agent as measured by SDS-PAGE; (c) an apparent molecular weight of about 12,500 daltons under reducing conditions as measured by SDS-PAGE; (d) does not compete with epidermal growth factor for receptor binding; (e) induces dose-dependent formation of large colonies having a size of greater than 3,100 μm 2 of NRK 49F cells in a soft agar assay when activated by epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-α); and being purified to the extent that (1) it does not itself induce NRK cells to form said large colonies in soft agar and (2) a single band with an apparent molecular weight of about 12,500 daltons is shown on SDS-PAGE under reducing conditions and a single band with an apparent molecular weight of about 25,000 is shown under non-reducing conditions; and a pharmaceutically acceptable carrier therefor.

Claim 7

A method of promoting proliferation of cells in an animal comprising: administering to the animal a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable carrier, and a polypeptide that (a) is active in the TGF-beta assay, (b) is a dimer having an approximate molecular weight of about 25,000-26,000 daltons as determined by SDS-PAGE, and (c) is purified, wherein said polypeptide and activating agent are present in amounts sufficient to promote cell proliferation.

Claim 8

A method of promoting proliferation of cells in an animal comprising: administering to the animal a composition comprising a TGF-beta activating agent, a pharmaceutically acceptable carrier, and a polypeptide that (a) is active in the TGF-beta assay, (b) is a dimer having an approximate molecular weight of about 25,000-26,000 daltons as determined by SDS-PAGE, and (c) is purified, wherein said polypeptide and activating agent are present in amounts sufficient to promote cell proliferation.