30. Cancer 2

MIT OpenCourseWare2 minutes read

Smoking is linked to increased lung cancer rates, especially in women, but rates are decreasing as fewer women smoke. Genes related to proliferation, cell death, and motility contribute to cancer development, with oncogenes like RAS playing a role in cell transformation and uncontrolled proliferation.

Insights

  • Smoking is strongly linked to increased rates of lung cancer in both men and women, with a significant impact on overall cancer statistics, especially for women where lung cancer rates have surpassed breast cancer due to smoking.
  • Understanding the role of oncogenes and tumor suppressor genes, such as the RB gene, is crucial in cancer development, as mutations in these genes can lead to uncontrolled cell division and proliferation, highlighting the importance of genetic factors in cancer progression and potential treatment strategies.

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Recent questions

  • How does smoking contribute to cancer?

    Smoking introduces carcinogens and mutagens into the body, leading to cancer development. Environmental carcinogens like cigarette smoke and chemicals can cause mutations and cancer. Non-mutagenic carcinogens like alcohol and asbestos can also lead to cancer by causing tissue damage.

  • What role do oncogenes play in cancer development?

    Oncogenes, like RAS, dominantly transform cells through gain-of-function mutations, with about 300 known oncogenes in the human genome. Oncogenes can be altered through subtle mutations, gene amplifications, or gene rearrangements like translocations. Single mutations may not be sufficient for cancer development, as multiple mutations are likely needed for full-blown cancer.

  • How do tumor suppressor genes regulate cell division?

    Tumor suppressor genes, like the RB gene, negatively regulate cell proliferation and are mutated in many cancer cells. The RB gene encodes the pRB protein, which controls the cell cycle by blocking the transition from G1 to S phase. RB protein can be inactivated through phosphorylation by kinases, leading to the release of the cell cycle control.

  • What is the significance of mutations in critical genes for cancer?

    Mutations in critical genes due to replication errors or chromosome segregation issues contribute to cancer development. Cancer evolves from normal cells through mutations in genes related to proliferation, cell death, angiogenesis, motility, and invasiveness. Understanding cancer genes through genome sequencing aids in diagnosis, prognosis, and personalized treatment.

  • How do replication errors contribute to cancer development?

    Mutations in critical genes due to replication errors or chromosome segregation issues contribute to cancer development. Cancer evolves from normal cells through mutations in genes related to proliferation, cell death, angiogenesis, motility, and invasiveness. Understanding cancer genes through genome sequencing aids in diagnosis, prognosis, and personalized treatment.

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Summary

00:00

"Cancer Discussion: Smoking, Mutations, and Genes"

  • Tyler Jacks announces a continuation of the discussion on cancer, with an upcoming exam and office hours for questions.
  • Smoking statistics show a correlation between increased smoking rates and lung cancer rates in men and women.
  • Lung cancer rates in women have surpassed breast cancer due to smoking, but rates are now decreasing as fewer women smoke.
  • Smoking introduces carcinogens and mutagens into the body, leading to cancer development.
  • Environmental carcinogens like cigarette smoke and chemicals can cause mutations and cancer.
  • Non-mutagenic carcinogens like alcohol and asbestos can also lead to cancer by causing tissue damage.
  • Mutations in critical genes due to replication errors or chromosome segregation issues contribute to cancer development.
  • Cancer evolves from normal cells through mutations in genes related to proliferation, cell death, angiogenesis, motility, and invasiveness.
  • Understanding cancer genes through genome sequencing aids in diagnosis, prognosis, and personalized treatment.
  • Oncogenes, identified through studies on oncogenic viruses like Rous sarcoma virus, play a role in cancer development and personalized medicine advancements.

19:04

"Oncogenes: Transforming Cells Through Genetic Mutations"

  • The SRC gene, responsible for sarcoma, can induce transformation when added to a process.
  • In 1975, UCSF investigators Bishop and Varmus discovered a homologue of the SRC gene in chicken cells, suggesting the gene's cellular origin.
  • SRC gene's presence in human cells was surprising, leading to Bishop and Varmus winning the Nobel Prize in 1989.
  • Weinberg's experiment with bladder cancer DNA introduced into immortalized mouse cells showed transformation and tumorigenic potential due to a mutant RAS gene.
  • The mutant RAS gene had a single nucleotide change causing constitutive signaling for abnormal cell division.
  • RAS is part of a signaling cascade involving receptor molecules, growth factors, kinases, and transcription factors.
  • Oncogenes, like RAS, dominantly transform cells through gain-of-function mutations, with about 300 known oncogenes in the human genome.
  • Oncogenes can be altered through subtle mutations, gene amplifications, or gene rearrangements like translocations.
  • Single mutations may not be sufficient for cancer development, as multiple mutations are likely needed for full-blown cancer.
  • Cancer cells have defects in both go signals (oncogenes) for cell division and stop signals, leading to uncontrolled proliferation.

37:35

Genes in Cancer Development: Oncogenes vs Tumor Suppressors

  • Oncogenes and tumor suppressor genes are two classes of genes involved in cell division regulation.
  • Tumor suppressor genes, like the RB gene, negatively regulate cell proliferation and are mutated in many cancer cells.
  • The RB gene encodes the pRB protein, which controls the cell cycle by blocking the transition from G1 to S phase.
  • RB protein can be inactivated through phosphorylation by kinases, leading to the release of the cell cycle control.
  • Tumor suppressor genes require two hits or mutational events to inactivate both copies of the gene, leading to cancer development.
  • Familial cancer syndromes, like familial retinoblastoma, are caused by inherited mutations in genes like RB, increasing the predisposition to cancer development.
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