Invention:
This invention is directed to a monoclonal antibody that recognizes human ING4 in its native form. The invention is also directed to a hybridoma cell line that produces the monoclonal antibody, and to methods of diagnosing cancer using the antibody.
Background:
ING4 is a member of the ING tumor suppressor family and has been shown to play a role in many cancer-related cellular processes, including, cell proliferation, apoptosis, migration, angiogenesis, contact inhibition, DNA damage response, and hypoxia. Gene deletion or reduced expression of ING4 has been reported in various cancers including glioma, breast cancer, head and neck carcinoma, melanoma, hepatocellular carcinoma, gastric carcinoma, colon cancer, and lung cancer, implicating a tumor suppressive role of ING4 in diverse tissue types. ING4 null mice, however, do not show increased spontaneous tumor formation, suggesting that ING4 deficiency alone may not be sufficient to initiate tumorigenesis. ING4 was identified in a genetic screen for candidate tumor suppressors that could suppress loss of contact inhibition in tissue culture. Subsequently, it was shown that ING4 suppressed T47D breast cancer cell growth in soft agar and MYC-initiated mammary hyperplasia in a mouse model, providing evidence for the ING4 tumor suppressor function in breast cancer. Recently, it was reported that 16.5% of breast tumors harbored an ING4 gene deletion, suggesting a tumor suppressive role of ING4 in at least a subset of breast cancer.
Functionally, ING4 is characterized as a transcription regulator with a mechanism involving chromatin remodeling. ING4 contains a plant homeodomain (PHD) finger motif conserved among the ING family members and other transcription factors. ING4 binds to tri-methylated histone H3 at lysine 4 (H3K4me3) via the PHD. In addition, ING4 co-purifies with the HBO1/JADE histone acetyltransferase (HAT) complex, supporting a role of ING4 in chromatin modification. As H3K4me3 and HAT are generally associated with active transcription, ING4 is known to activate gene transcription in response to DNA damage. In glioma and melanoma cancer models, ING4 repressed several NF-κB-target genes, thereby attenuating tumor angiogenesis and growth. Additionally, ING4 has been shown to represses NF-κB in breast cancer cells.
A need exists for anti-ING4 antibodies having unique genetic and amino acid structures, including unique binding and functional characteristics. The development of new anti-ING4 monoclonal antibodies and hybridoma cells lines that produce such monoclonal antibodies would be a valuable tool for the effective diagnosis of various cancers.
Status: US issued patent #9,193,785
