Cancer Replication and Telomere Mechanisms
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Questions and Answers

Which cancers are commonly associated with TERT promoter mutations?

  • Colon cancer
  • Breast cancer
  • Glioblastoma (correct)
  • Merkel cell carcinoma

Higher levels of TERT expression are associated with better survival rates in bladder carcinoma patients.

False (B)

Name one consequence of having too much telomerase activity.

Cancer

A correlation between telomerase over expression and __________ exists in human cancer.

<p>cancer development</p> Signup and view all the answers

Match the following cancers with their association with TERT mutations:

<p>Glioblastoma = Found Breast cancer = Not Found Bladder carcinoma = Found Colon cancer = Not Found</p> Signup and view all the answers

What is the first step towards carcinogenesis in cells?

<p>Immortalization (D)</p> Signup and view all the answers

Transformed cells are dependent on serum for growth.

<p>False (B)</p> Signup and view all the answers

What process occurs when telomeres become too short?

<p>Senescence or apoptosis</p> Signup and view all the answers

The protective ends of linear chromosomes are called __________.

<p>telomeres</p> Signup and view all the answers

During which phase do the majority of primary cells die?

<p>Crisis (C)</p> Signup and view all the answers

Match the following terms with their descriptions:

<p>Primary Cell = Normal cell with limited division Immortalized Cell = Unlimited proliferation in vitro, not malignant Transformed Cell = Malignant cell that can form tumors Metastases = Mobile tumorigenic cells that spread</p> Signup and view all the answers

What characterizes transformed cells?

<p>Independent of contact inhibition and can change shape (B)</p> Signup and view all the answers

Immortalized cells are equivalent to malignant cells in vivo.

<p>False (B)</p> Signup and view all the answers

What role does telomerase play in cells that require extensive proliferation?

<p>It adds repetitive six-base sequences to telomeres. (D)</p> Signup and view all the answers

The short single-stranded DNA at the telomere does not play any role in protecting chromosome ends.

<p>False (B)</p> Signup and view all the answers

What happens to chromosomes when telomere loss occurs?

<p>Chromosomes undergo end-to-end fusion leading to apoptosis or cell death.</p> Signup and view all the answers

Telomerase is a reverse transcriptase known as _____.

<p>TERT</p> Signup and view all the answers

What is the main consequence of telomerase loss of function?

<p>Genomic instability and cell death (D)</p> Signup and view all the answers

Telomerase is expressed at low levels in invasive cancers.

<p>False (B)</p> Signup and view all the answers

What is the effect of high telomerase activity in cancer cells?

<p>It allows cancer cells to proliferate indefinitely.</p> Signup and view all the answers

Dyskeratosis congenita is caused by a mutation in one _____ allele.

<p>hTER</p> Signup and view all the answers

Which protein is linked to increased telomerase activity through an oncogenic effect?

<p>Myc (C)</p> Signup and view all the answers

Long telomeres have fewer binding proteins, allowing stronger inhibition of telomerase.

<p>False (B)</p> Signup and view all the answers

What is the primary function of TERT?

<p>To bind RNA and use it as a template to extend telomeric DNA.</p> Signup and view all the answers

Shortened telomeres can lead to increased _____ risk.

<p>cancer</p> Signup and view all the answers

The creation of a protective t-loop involves the binding of single-stranded DNA to what type of region?

<p>Double-stranded region (C)</p> Signup and view all the answers

Flashcards

TERT Promoter Mutations

These mutations in the TERT promoter region are frequently found in melanoma and other cancers, but not in normal cells. They contribute to cancer development.

Telomerase Overexpression and Cancer

A strong correlation exists between increased levels of telomerase activity (overexpression) and the development of several types of cancer.

TERT Promoter Mutations: Not Universal

While TERT promoter mutations are common in some cancers like melanoma, they are not found in all cancers. For example, they are rarely seen in colon or breast cancer.

TERT Expression and Survival

In bladder carcinoma, patients with lower levels of telomerase expression tend to have better survival rates compared to those with higher levels.

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Telomerase Balance

Telomerase plays a crucial role in maintaining a balance between cell division and aging. Too little telomerase leads to premature aging and weakened immune systems, while too much is associated with cancer development.

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Cancer Cell Immortality

Cancer cells have the ability to replicate indefinitely, unlike normal cells that have a limited lifespan.

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Primary Cells

Cells taken directly from tissue and cultured. These cells have a limited capacity for division.

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Crisis (Cancer)

A stage in cancer development where most cells die, but a few survive and start overexpressing telomerase.

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Immortalization

Cells acquire the ability to divide indefinitely, but still adhere to the plate and are regulated by contact inhibition.

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Transformation (Cancer)

Cells become independent of growth factors, contact inhibition, and acquire the ability to form tumors when injected into animals.

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Metastases

Cancer cells become mobile and spread to distant locations in the body, forming new tumors.

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Telomeres

Protective caps at the ends of chromosomes that shorten with each cell division.

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Telomerase

An enzyme that can lengthen telomeres, allowing cells to divide indefinitely.

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Telomere Loss

The shortening of protective caps at the ends of chromosomes, leading to chromosome fusion, apoptosis, or cell death.

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Reverse Transcriptase

An enzyme that synthesizes DNA from an RNA template.

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Telomere-Binding Proteins

Proteins that bind to the double-stranded portion of telomeres, regulating telomerase activity and protecting chromosome ends.

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T-loop

A protective loop structure formed by telomere-binding proteins and single-stranded DNA at the end of a chromosome.

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Dyskeratosis Congenita

A genetic disorder caused by mutations in telomerase, leading to shortened telomeres and various health issues.

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Telomerase Gain of Function (GOF)

Increased telomerase activity in cancer cells, enabling unlimited cell division.

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Telomerase in Cancer Cells

Telomerase is highly expressed in most cancerous cells, contributing to their uncontrolled growth and proliferation.

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TERT (Telomerase Reverse Transcriptase)

The catalytic subunit of telomerase, responsible for extending telomeres.

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Epigenetic Switch

A change in gene expression without altering the DNA sequence itself, often involving modifications to DNA or associated proteins.

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Myc TF

An oncogene that upregulates telomerase expression, promoting cancer cell growth.

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Undifferentiated Stem-Like Phenotype

A state of cells that have not yet specialized into specific cell types, often associated with cancer cells.

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Telomere Length Regulation

The process of maintaining telomere length within a healthy range, preventing excessive shortening or lengthening.

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Telomerase Loss of Function (LOF)

Reduced or absent telomerase activity, leading to shortened telomeres and various cell problems, including premature aging and cancer.

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Study Notes

Cancer Replication and Telomeres

  • Cancer cells replicate immortally, a crucial characteristic.
  • Experimental cancer progression in cell culture demonstrates sequential stages: primary cells, crisis, immortalization, transformation, and metastasis.
  • Primary cells have limited divisions; crisis marks cell death; immortalized cells continue dividing but remain attached to the plate and require serum; transformed cells grow without contact inhibition or serum; metastasized cells migrate to form new colonies.

Telomeres and Telomerase

  • Telomeres are protective caps on chromosome ends, crucial for replication regulation.
  • Telomeres shorten progressively (~150-200 base pairs per division) due to limitations of DNA polymerase.
  • Shortened telomeres lead to senescence (stopping division) or apoptosis (cell death).
  • Telomerase, active in rapidly dividing cells, adds six-base repetitive sequences (TTAGGG) to restore telomere length.

Telomerase Mechanism

  • Telomerase, a reverse transcriptase (TERT), uses an RNA template to extend telomeric DNA.
  • Telomere-binding proteins regulate telomerase activity; their presence depends on telomere length.
  • Short telomeres have weak inhibition of telomerase; long telomeres have strong inhibition.
  • This delicate balance maintains telomere length.
  • Telomere-binding proteins, along with single-stranded DNA, form a protective t-loop, preventing chromosome damage.

Telomerase and Cancer

  • Telomerase is highly expressed (80-90%) in invasive cancers.
  • Telomerase knock-out inhibits cancer cell growth and reduces metastasis.
  • Myc, an oncogene, upregulates telomerase.
  • High telomerase levels promote undifferentiated, stem-like cancer cell traits.

TERT as an Oncogene

  • TERT, a subunit of telomerase, can function as an oncogene through promoter mutations (e.g., -124 position).
  • These mutations increase TERT expression and telomerase activity.
  • This is common in some cancers, like melanoma but not all.

Telomerase and Disease

  • Insufficient telomerase activity is linked to reduced stem cell numbers, weakened immunity, premature aging, and increased cancer risk.
  • Excessive telomerase activity is directly implicated in cancer development.
  • Lower TERT expression correlates with better disease-specific survival in some cancers, such as bladder carcinoma.

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Description

Explore the pivotal role of cancer cell replication and the biology of telomeres in cellular aging. This quiz covers the stages of cancer progression, the function of telomeres, and the mechanisms of telomerase in maintaining chromosomal integrity. Test your understanding of these critical concepts in oncology and cellular biology.

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