Abstract: The instant invention relates to the determination that constitutively nearly silent GrB locus in human breast carcinoma and osteosarcoma cells activated upon retinoblastoma protein (pRB)-induced growth arrest owing to the usage of an alternative promoter/transcription start site. Cloned novel cDNA from the locus adds 34 amino acid residues to the N-terminus of GrB zymogen. The alternate product has been designated as GrB-NIC. Tumor cells with accumulated endogenous GrB-NIC, whose mature form was identical to lymphocyte GrB but with a distinctive glycosylation pattern, undergoes post-growth-arrest apoptosis that occurs concurrently with pRB cleavage, and are capable of inducing rapid apoptosis of bystander pRB? tumor cells. Expression of GrB-NIC is also observed in malignant cells of other types as well as in normal non-immune cells upon cell differentiation, especially in differentiating and differentiated neural cells.

Abstract: The instant invention relates to the determination that constitutively nearly silent GrB locus in human breast carcinoma and osteosarcoma cells activated upon retinoblastoma protein (pRB)-induced growth arrest owing to the usage of an alternative promoter/transcription start site. Cloned novel cDNA from the locus adds 34 amino acid residues to the N-terminus of GrB zymogen. The alternate product has been designated as GrB-NIC. Tumor cells with accumulated endogenous GrB-NIC, whose mature form was identical to lymphocyte GrB but with a distinctive glycosylation pattern, undergoes post-growth-arrest apoptosis that occurs concurrently with pRB cleavage, and are capable of inducing rapid apoptosis of bystander pRB− tumor cells. Expression of GrB-NIC is also observed in malignant cells of other types as well as in normal non-immune cells upon cell differentiation, especially in differentiating and differentiated neural cells.

Abstract: Disclosed are modified broad-spectrum retinoblastoma tumor suppressor proteins that have at least the same, and in most cases higher biological activity than the corresponding wild-type retinoblastoma tumor suppressor protein. Exemplary modified retinoblastoma tumor suppressor proteins have a modified N-terminal region, in particular comprising one or more deletions and/or mutations. Also disclosed are methods of making and using the modified retinoblastoma tumor suppressor proteins, particularly in circumstances where inhibition of cell growth is desired. Thus the present disclosure provides methods for treating diseases, as exemplified by, but not limited to cancer, that are characterized by abnormal cellular proliferation.

Abstract: The present invention relates to a broad-spectrum tumor suppressor gene and the protein expressed by that gene in appropriate host cells. The protein is a second in-frame AUG codon-initiated retinoblasoma protein of about 94 kD relative molecular mass. The present invention also relates to methods of treating a mammal having a disease or disorder characterized by abnormal cellular proliferation, such as a tumor or cancer and methods of treating abnormally proliferating cells, such as tumor or cancer cells. Treatment is accomplished by inserting a host cell compatible p94.sup.RB expression vector or an effective amount of p94.sup.RB protein into a cell or cells in need of treatment.

Abstract: The present invention relates to a broad-spectrum tumor suppressor gene and the protein expressed by that gene in appropriate host cells. The protein is a second in-frame AUG codon-initiated retinoblasoma protein of about 94 kD relative molecular mass. The present invention also relates to methods of treating a mammal having a disease or disorder characterized by abnormal cellular proliferation, such as a tumor or cancer and methods of treating abnormally proliferating cells, such as tumor or cancer cells. Treatment is accomplished by inserting a host cell compatible p94.sup.RB expression vector or an effective amount of p94.sup.RB protein into a cell or cells in need of treatment.