We observed notable differences among domain specific anti-IGF1R antibodies with regards to their ability to 1) inhibit ligand binding and ligand-induced activation of IGF1R and INSR, 2) downregulate IGF1R and INSR expression, 3) inhibit cell proliferation and tumor growth, and 4) activate IGF1R and INSR in the absence of ligand. The gene discussed is INSR; the disease is neoplasm.