Telomerase Wiki Flashcards
In vitro, when cells approach the Hayflick limit, the time to senescence can be extended by inactivating the tumor suppressor proteins - p53 and Retinoblastoma protein (pRb).
What is the Hayflick limit?
The Hayflick limit or Hayflick phenomenon is the number of times a normal human cell population will divide until cell division stops. Empirical evidence shows that the telomeres associated with each cell’s DNA will get slightly shorter with each new cell division until they shorten to a critical length
How can the Hayflick limit be extended?
In vitro, when cells approach the Hayflick limit, the time to senescence can be extended by inactivating the tumor suppressor proteins - p53 and Retinoblastoma protein (pRb).
What is one good example of immortal cancer cells?
HeLa cells.
HeLa /ˈhiːlɑː/ (also Hela or hela) is a cell type in an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line.[1] The line was derived from cervical cancer cells taken on February 8, 1951[2] from Henrietta Lacks, a patient who died of her cancer on October 4, 1951. The cell line was found to be remarkably durable and prolific which warrants its extensive use in scientific research.[3][4]
The exact changes that allow for immortal cancer cells to develop is unknown. What alterations are known to be required?
TERT (Telomerase reverse transcriptase) activation, loss of p53 pathway function, loss of pRb pathway function, activation of the Ras or myc proto-oncogenes, and aberration of the PP2A protein phosphatase.
90% of human tumours exhibit telomerase activation. Of the remaining 10%, most employ what alternative method of immortality?
Alternative Lengthening of Telomeres (ALT).
About 5–10% of human cancers activate the alternative lengthening of telomeres (ALT) pathway, which relies on recombination-mediated elongation.
What is ALT?
Alternative Lengthening of Telomeres (ALT).
Telomerase is a good biomarker for cancer detection because most human cancers cells express high levels of it. Telomerase activity can be identified by what?
Telomerase is a good biomarker for cancer detection because most human cancers cells express high levels of it. Telomerase activity can be identified by its catalytic protein domain (hTERT)
TERT activation, loss of p53 pathway function, loss of pRb pathway function, activation of the Ras or myc proto-oncogenes, and aberration of the PP2A protein phosphatase are all requirements for the development of what?
Immortal cancer cells.
What is hTERT?
Telomerase is a good biomarker for cancer detection because most human cancers cells express high levels of it. Telomerase activity can be identified by its catalytic protein domain (hTERT).
The expression of hTERT can also be used to distinguish benign tumors from malignant tumors. Malignant tumors have higher hTERT expression than benign tumors. Real-time reverse transcription polymerase chain reaction (RT-PCR) quantifying hTERT expression in various tumor samples verified this varying expression
What is Imetelstat?
Immunotherapy example for cancer that targets telomerases.
Imetelstat is a 13-mer oligonucleotide that acts as a direct telomerase inhibitor by antagonistically binding to the RNA template of telomerase (hTR).
What are the four ways to target telomerases in cancer treatment?
Drugs which are targeted for cells which highly express HTERT.
Immunotherapy which targets HTERT or the RNA template of telomerase (hTR): Imetelstat [a 13-mer oligonucleotide].
Telomerase vaccines: GRNVAC1: isolates dendritic cells and the RNA that codes for the telomerase protein and then puts them back into the patient to make cytotoxic T cells that kill telomerase-active cells.
Targeted apoptosis: oligoadenylated anti-telomerase antisense oligonucleotides and ribozymes [RNA molecules that are capable of catalyzing specific biochemical reactions, similar to the action of protein enzymes] to target telomerase RNA.
What is a 13-mer oligonucleotide that acts as a direct telomerase inhibitor by antagonistically binding to the RNA template of telomerase (hTR)?
Imetelstat.
