As a tumor suppressor induces senescence and prevents cancer
“. Dissecting the unique role of the retinoblastoma tumor suppressor for cell senescence,” online in Cancer Cell on April 13 The full quote is: Agustin Chicas, Xiaowo Wang, Zhang Chaolin, Mila McCurrach, Zhen Zhao, Ozlem Mert, Ross A. Dickins, Masashi Narita, Michael Zhang, W. Scott Lowe.To study the relative effects of each RB family member of senescence, Lowe’s team has created a series of short hairpin RNA (shRNA) molecules specifically cut single genes of the RB family when introduced into human cells with intact RB networks. The team then made an oncogene in these cells, which triggers normal cells stop dividing and Senesch so as part of a mechanism for fail-safe that prevents cancer.
RB exact mode of activity has been difficult to unravel because it is part of a multigene family that includes two other members that are structurally very similar to RB and have highly overlapping functions. Yet the activity of RB seem to be a most essential part of anti-cancer arsenal of cells than other RB family members, which are very rarely mutated in human cancers.
The team found that when RB was just off, the cells could not effectively subject to this process of oncogene-induced senescence. When these cells have lost RB activity, could not shut down DNA replication has begun to play out of control and has developed a genomic instability. “This aberrant process, when exacerbated by failures in other control mechanisms, lead to the development of malignant tumors,” said Agustin Chicas, Ph.D., a postdoctoral researcher working with Dr. Lowe and the principal investigator of the study .
“The results suggest that our team aims selective DNA replication genes during senescence is a fundamental activity of RB in tumor suppression,” says Lowe.
Further investigations showed that the key objective of the RB is a gene called cyclin E1, which is found to be overactive in many human tumors and is often associated with poor prognosis in patients. Its normal function is to stimulate DNA replication during the cell cycle and then is deleted by RB in senescent cells. The team showed that the loss of RB releases cyclin E1, allowing cells to escape senescence.
One of the cellular processes controlled by the RB family is cellular senescence, which is now known to act as a barrier against cancer. “So we hypothesized that the protein only goal RB and control of certain proteins associated with aging, which in turn must balance its role as a powerful tumor suppressor,” says Lowe.
“We discovered that a key function of RB in the suppression of cancer derives from its ability to induce cellular senescence, a stage of growth arrest in which cells no longer divide,” says Cold Spring Harbor Laboratory (CSHL) professor and researcher at HHMI Scott Lowe, Ph.D., the findings of his team are online in the journal Cancer Cell
Frequently mutated gene in humans is the (RB) reitnoblastoma gene, which controls a powerful tumor suppressor path. Mutations in the gene to turn off the large and complex path RB in virtually all tumor cells, causing alterations in a variety of cellular functions and eventually causing cancer. But which of these functions is essential for the activity of the tumor suppressor gene was uncertain.
