Current Molecular Medicine - Volume 6, Issue 7, 2006

OVERVIEW The concept that the retinoblastoma arises as a result of two discrete genetic hits in the same tumor suppressor gene has been in existence for greater than 20 years [1-4]. Cloning and analyses of the retinoblastoma tumor suppressor gene (Rb) revealed that this same tumor suppressor is mutated not only in retinoblastoma, but in a litany of other tumor types (e.g. bladder cancer, osteosarcoma, lung cancer a Read More

All forms of life on Earth share a common ancestry. As a consequence, Homo sapiens shares a large number of genes essential for the development and maintenance of multicellular life with "simple" animals, such as the fruit fly Drosophila melanogaster and the nematode worm Caenorhabdites elegans. Indeed, Drosophila and C. elegans have successfully been used to unravel fundamental mechanisms underlyin Read More

The retinoblastoma (RB) gene was the first tumor suppressor to be identified, and it continues to be the subject of intense scientific interest. Not only is the RB gene mutated in the rare eye tumor and some other cancers, the Rb protein is functionally inactivated in virtually all human cancers, suggesting that it plays a general role in cellular homeostasis. Rb initially was envisaged as a simple ‘on-off’ regulator of the cell cycle, a Read More

Regulators of the cell cycle machinery play a major role in modulating a variety of cellular phenomena including proliferation, quiescence, differentiation, senescence and apoptosis. Studies in the past decade have clearly established a role for the retinoblastoma tumor suppressor protein, Rb, and its primary downstream target E2F1, in the above processes. While the role of the Rb protein in the regulation of cell cy Read More

Deregulation of E2F transcriptional activity as a result of alterations in the p16INK4a-cyclin D1-Rb pathway is a hallmark of human cancer. E2F is a family of related factors that controls the expression of genes important for cell cycle progression as well as other processes such as apoptosis, DNA repair, and differentiation. Some E2F family members are associated with the activation of transcription and the promotion of prolif Read More

Since the discovery almost fifteen years ago that E2F transcription factors are key targets of the retinoblastoma protein (RB), studies of the E2F family have uncovered critical roles in the control of transcription, cell cycle and apoptosis. E2F proteins are encoded by at least eight genes, E2F1 through E2F8. While specific roles for individual E2Fs in mediating the effects of RB loss are emerging, it is also becoming clear that ther Read More

The retinoblastoma tumor suppressor (RB) is functionally inactivated at high frequency in human cancers. Based on the role of RB as a negative regulator of cell cycle this event would be expected to contribute to deregulated proliferation. However, evidence suggests that loss of RB not only mediates aberrant proliferation, but compromises the fidelity of cell cycle transitions leading to a breakdown in genome integrity. This re Read More

The RB gene was discovered 20 years ago because of its role in the childhood eye cancer retinoblastoma. However, surprisingly little progress was made in defining the role of RB protein in the retina. In the last two years, new models exploiting conditional deletion of the mouse Rb gene have altered this picture radically. These models provide insight into the first Rb function, the cell of origin of retinoblastoma, the window duri Read More

Lung cancer is the leading cause of cancer related deaths accounting for more deaths than breast, colon and prostate cancers combined. The Rb-p16 regulatory pathway plays an essential role in tumor suppression in the lung epithelium. This is evidenced by the nearly universal alterations in Rbp16 pathway components in lung cancer, and the increased incidence of pulmonary carcinomas in persons with germline Rb mutatio Read More

Infection with human papillomaviruses (HPVs) is a major public health burden worldwide and is associated with benign and malignant lesions of the skin and genital tract. HPV causes cervical cancer, which represents the second most prevalent cancer in women worldwide. Functions of the viral oncogenes E6 and E7 are essential for carcinogenesis and for support of the viral life cycle. We will begin by discussing the relationship Read More

Osteogenic sarcoma (osteosarcoma) is the most common primary tumor of bone. It accounts for approximately 19% of all malignant tumors of the bone. Of all the molecular targets altered during the genesis of osteosarcoma, the retinoblastoma gene (RB1) shows the highest frequency of inactivation. Published data from human osteosarcoma tumors and in vivo and in vitro model systems support a role for the retinoblasto Read More