Tumor and Stem Cell Biology Pocket Proteins Suppress Head and Neck Cancer

Head and neck squamous cell carcinomas (HNSCC) is a common cancer in humans long known to be caused by tobacco and alcohol use, but now an increasing percentage of HNSCC is recognized to be caused by the same human papillomaviruses (HPV) that cause cervical and other anogenital cancers. HPV-positive HNSCCs differ remarkably fromHPV-negativeHNSCCs in their clinical response andmolecular properties. From studies inmice, we know that E7 is the dominant HPV oncoprotein in head and neck cancer. E7 is best known for its ability to inactivate pRb, the product of the retinoblastoma tumor susceptibility gene. However, loss of pRb function does not fully account for potency of E7 in causing head and neck cancer. In this study, we characterized the cancer susceptibility ofmice deficient in the expression of pRb and either of two related "pocket" proteins, p107 and p130, that are also inactivated by E7. pRb/p107-deficientmice developed head and neck cancer as frequently as doHPV16 E7 transgenic mice. The head and neck epithelia of the pRb/p107-deficient mice also displayed the same acute phenotypes and biomarker readouts as observed in the epithelia of E7 transgenicmice.Mice deficient for pRb and p130 in their head and neck epithelia showed intermediate acute and tumor phenotypes. We conclude that pRb and p107 act together to efficiently suppress head and neck cancer and are, therefore, highly relevant targets of HPV-16 E7 in its contribution to HPV-positive HNSCC. Cancer Res; 72(5); 1280–9. 2012 AACR.