Passage 1: Nucleic acid structure and genetic regulation
Retinoblastoma is a rare eye cancer that primarily affects young children. It is
caused by mutations in the RB1 gene, which is a tumor suppressor gene responsible
for regulating cell division in the retina. The RB1 gene encodes the retinoblastoma
protein (pRB), which plays a crucial role in the control of the cell cycle.
In normal cells, pRB is phosphorylated by cyclin-dependent kinases (CDKs) during
the G1 phase of the cell cycle, allowing the cell to progress to the S phase. However,
when the RB1 gene is mutated, it produces a non-functional pRB that cannot
be phosphorylated, leading to uncontrolled cell division and the formation of
retinoblastoma tumors.
Recent studies have explored the potential of using recombinant DNA technology
to introduce a functional RB1 gene into retinoblastoma cells. One approach involves
the use of adenoviral vectors to deliver the RB1 gene to the affected cells. The
introduced RB1 gene is placed under the control of a strong promoter, ensuring high
levels of expression. Once the functional pRB is produced, it can regulate the cell
cycle and suppress tumor growth.
Another area of research focuses on the development of small molecules that
can mimic the function of pRB. These molecules, known as CDK inhibitors, can
prevent the phosphorylation of pRB by CDKs, effectively halting the cell cycle and
preventing the proliferation of retinoblastoma cells. Several CDK inhibitors, such
as palbociclib and abemaciclib, have shown promise in preclinical studies and are
currently being investigated in clinical trials.
Understanding the molecular basis of retinoblastoma has also led to the
identification of biomarkers that can aid in the early detection and monitoring of
the disease. One such biomarker is the expression level of the RB1 gene, which can
be assessed using quantitative reverse transcription-polymerase chain reaction
(qRT-PCR). Low levels of RB1 expression may indicate the presence of mutations
and an increased risk of developing retinoblastoma.
CDK inhibitors, such as palbociclib and abemaciclib, are being investigated as
potential treatments for retinoblastoma because they:
A) Promote the phosphorylation of pRB by CDKs
B) Prevent the phosphorylation of pRB by CDKs, halting the cell cycle
C) Stimulate the expression of the RB1 gene in retinoblastoma cells
D) Enhance the activity of cyclin-dependent kinases in normal retinal cells
Correct Answer: B
CDK inhibitors, such as palbociclib and abemaciclib, are being investigated as
potential treatments for retinoblastoma because they prevent the phosphorylation
of pRB by CDKs. By preventing this phosphorylation, these inhibitors halt the cell
cycle and prevent the proliferation of retinoblastoma cells.