Biology of Cancer

Student's Name
Professor's Name
Class Information
Date
Cancer Biology
1. Dr. Richard Baer
A.
The expression of large T antigen in HDFs (human diploid fibroblasts) profoundly affects the processes of replicative senescence and genetic catastrophe. Large T antigen is a viral protein encoded by Simian Virus 40 (SV40 2-4) that can bind and inactivate tumor suppressor proteins like p53 and pRb (Moens & MacDonald). In normal HDFs, replicative senescence is a phenomenon where cells undergo a limited number of divisions due to the progressive shortening of telomeres and DNA sequences at the ends of chromosomes. When a large T antigen is introduced, it inactivates pRb, allowing cells to bypass the cell cycle checkpoint and continue to divide. However, large T antigen does not prevent telomere shortening, leading to critically shortened and dysfunctional telomeres. This sets the stage for genetic catastrophe, where cells may undergo chromosomal instability, aneuploidy, and accumulate DNA damage. While these cells may continue to replicate, they often harbor significant chromosomal aberrations, which can affect their function and potentially contribute to cancer development. Immortalized cells by large T antigen generally exhibit an abnormal karyotype, with a mix of numerical and structural chromosomal alterations that reflect their genomic instability.
B
Constitutive expression of TERT (telomerase reverse transcriptase) in HDFs has a different effect on replicative senescence and genetic catastrophe. TERT, serving as the catalytic component of telomerase, has a pivotal role in extending telomeres. In regular human diploid fibroblasts (HDFs), replicative senescence ensues as telomeric DNA gradually diminishes with each cell division. The introduction of TERT enables cells to extend their telomeres, counteracting the shortening process and permitting more cell divisions. TERT-immortalized cells maintain longer telomeres, preventing telomere-related senescence (Dratwa et al. 1). However, they are not entirely immune to genetic catastrophe, as other contributing factors can lead to DNA damage accumulation over time. However, unlike large T antigens, the genetic disaster in TERT-immortalized cells is not directly linked to telomere shortening. Karyotypes of TERT-immortalized cells may appear more stable and resemble the diploid, euploid state typical of normal cells. This stability is a result of maintaining telomere length and minimizing telomere dysfunction-related genetic chaos.
2. Dr. Allison Taylor
A
Depleting Mad2 causes premature sister chromatid separation by disrupting the spindle assembly checkpoint (SAC) and interfering with kinetochore-microtubule attachments. This leads to chromosome mis-segregation and aneuploidy. Another gene, BubR1, when depleted, can also disrupt the SAC, resulting in similar premature chromatid separation.
B
B-1
"MIN" stands for Microsatellite Instability, while "CIN" stands for Chromosomal Instability.
B-2
Microsatellite instability (MIN) involves alterations in the length of short, repetitive DNA sequences (microsatellites) in a cell's genome, often caused by defects in DNA mismatch repair mechanisms. This instability results in changes in microsatellite length and...