From stem cells to cancer : the role of the RB family in cell cycle control and differentiation
Abstract/Contents
- Abstract
- Embryonic stem cells (ESCs) hold great therapeutic potential, but the regulation of their self-renewal and pluripotency is still not fully understood. Furthermore, ESCs display many similarities to cancer cells, including rapid proliferation and tumorigenic potential, making it critical to understand the basic properties of these cells. The RB family, consisting of RB, p107, and p130, are critical regulators of functions such as cell cycle progression, apoptosis, and differentiation that must be tightly regulated throughout development. Here, we used loss and gain of function experiments to understand the role of the RB family in regulating key properties of ESCs. In hESCs, the RB family is critical for self-renewal and survival. hESCs overexpressing RB arrest in the cell cycle and undergo spontaneous differentiation and apoptosis. Loss of RB family function in hESCs results in decreased self-renewal ability and a loss of pluripotency, as these cells display a defect in their differentiation capacity. hESCs undergo a G2/M arrest and apoptosis through activation of the p53 pathway and the cell cycle inhibitor p21 upon loss of RB family function. In contrast to hESCs, mESCS triple knockout (TKO) for the RB family are largely normal. However, both mouse and human ESCs display genomic instability upon loss of RB family function, highlighting a key function that is conserved between both species. The RB family also regulates many functions that are critical for tumor suppression. We investigated whether RB retains its tumor suppressive ability in cancer cells by re-introducing RB into Rb-/-; p53-/- small cell lung cancer (SCLC) tumors cells. Re-introduction of RB resulted in decreased growth and an increase in differentiation, similar to that seen in hESCs. Thus, the RB pathway is an important regulator of self-renewal and differentiation in both hESCs and SCLC.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Imam, Jamie Francine Conklin |
|---|---|
| Associated with | Stanford University, Department of Genetics |
| Primary advisor | Sage, Julien |
| Thesis advisor | Sage, Julien |
| Thesis advisor | Baker, Julie, (Professor of genetics) |
| Thesis advisor | Reijo Pera, Renee |
| Thesis advisor | Stearns, Tim |
| Advisor | Baker, Julie, (Professor of genetics) |
| Advisor | Reijo Pera, Renee |
| Advisor | Stearns, Tim |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jamie Francine Conklin Imam. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph. D.)--Stanford University, 2011. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Jamie Francine Conklin Imam
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...