Proto Oncogenes Can Be Converted to Oncogenes

In 1972, R. J. Huebner and G. J. Todaro suggested that mutations or genetic rearrangements of proto-oncogenes by carcinogens or viruses might alter the normally regulated function of these genes, converting them into potent cancer-causing oncogenes (Figure 22-2). Considerable evidence supporting this hypothesis accumulated in subsequent years. For example, some malignantly transformed cells contain multiple copies of cellular oncogenes, resulting in increased production of onco-gene products. Such amplification of cellular oncogenes has been observed in cells from various types of human cancers. Several groups have identified c-myc oncogenes in homogeneously staining regions (HSRs) of chromosomes from can-

Normal cells

Transformed cells

Normal cells

Transformed cells

Conversion Proto Oncogene Oncogene

(T) Qualitatively altered, hyperactive proteins (2) Quantitative alterations (gene amplification or translocation) resulting in increased or decreased levels of products

Essential growth controlling proteins Growth factors Growth-factor receptors Signal transducers Intranuclear factors Regulators of programmed cell death

(T) Qualitatively altered, hyperactive proteins (2) Quantitative alterations (gene amplification or translocation) resulting in increased or decreased levels of products

FIGURE 22-2

Conversion of proto-oncogenes into oncogenes can involve mutation, resulting in production of qualitatively different gene products, or DNA amplification or translocation, resulting in increased or decreased expression of gene products.

cer cells; these HSRs represent long tandem arrays of amplified genes.

In addition, some cancer cells exhibit chromosomal translocations, usually the movement of a proto-oncogene from one chromosomal site to another (Figure 22-3). In many cases of Burkitt's lymphoma, for example, c-myc is moved from its normal position on chromosome 8 to a position near the immunoglobulin heavy-chain enhancer on chromosome 14. As a result of this translocation, synthesis of the c-Myc protein, which functions as a transcription factor, increases.

Mutation in proto-oncogenes also has been associated with cellular transformation, and it may be a major mechanism by which chemical carcinogens or x-irradiation convert a proto-oncogene into a cancer-inducing oncogene. For instance, single-point mutations in c-ras have been detected in a significant fraction of several human cancers, including carcinomas of the bladder, colon, and lung. Some of these mutations appear to reduce the ability of Ras to associate with GTPase-stimulating proteins, thus prolonging the growth-activated state of Ras.

Viral integration into the host-cell genome may in itself serve to convert a proto-oncogene into a transforming onco gene. For example, avian leukosis virus (ALV) is a retrovirus that does not carry any viral oncogenes and yet is able to transform B cells into lymphomas. This particular retrovirus has been shown to integrate within the c-myc proto-oncogene, which contains three exons. Exon 1 of c-myc has an unknown function; exons 2 and 3 encode the Myc protein. Insertion of AVL between exon 1 and exon 2 has been shown in some cases to allow the provirus promoter to increase transcription of exons 2 and 3, resulting in increased synthesis of c-Myc.

A variety of tumors have been shown to express significantly increased levels of growth factors or growth-factor

(a) Chronic myelogenous leukemia

(a) Chronic myelogenous leukemia

Chromosome That Expresses Leukemia
w w 9

w

Q

N

fi

m

Philadelphia chromosome

FIGURE 22-3

FIGURE 22-3

Translocation Philadephia Exon

Ch c-myc

Chromosomal translocations in (a) chronic myelogenous leukemia (CML) and (b) Burkitt's lymphoma. Leukemic cells from all patients with CML contain the so-called Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22. Cancer cells from some patients with Burkitt's lymphoma exhibit a translocation that moves part of chromosome 8 to chromosome 14. It is now known that this translocation involves c-myc, a cellular oncogene. Abnormalities such as these are detected by banding analysis of metaphase chromosomes. Normal chromosomes are shown on the left, and translocated chromosomes on the right.

Ch c-myc

Chromosomal translocations in (a) chronic myelogenous leukemia (CML) and (b) Burkitt's lymphoma. Leukemic cells from all patients with CML contain the so-called Philadelphia chromosome, which results from a translocation between chromosomes 9 and 22. Cancer cells from some patients with Burkitt's lymphoma exhibit a translocation that moves part of chromosome 8 to chromosome 14. It is now known that this translocation involves c-myc, a cellular oncogene. Abnormalities such as these are detected by banding analysis of metaphase chromosomes. Normal chromosomes are shown on the left, and translocated chromosomes on the right.

receptors. Expression of the receptor for epidermal growth factor, which is encoded by c-erbB, has been shown to be amplified in many cancer cells. And in breast cancer, increased synthesis of the growth-factor receptor encoded by c-neu has been linked with a poor prognosis.

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Responses

  • angelika kastner
    How can protooncogenes be converted to oncogenes?
    8 years ago
  • sophia
    How viruses covert protooncogenes into oncogenes?
    8 years ago
  • Uwe
    How myc protooncogene is converted to oncogene?
    8 years ago
  • orla watson
    How myc protoncogene converted to oncogene?
    8 years ago
  • KEIR
    What virus is involved in the conversion of proto oncogene to oncogene?
    8 years ago
  • saradas
    What type of mutation can convert protooncogenes into oncogenes?
    7 years ago
  • daisy
    How proto oncogene is converted to oncogene?
    3 years ago
  • vera
    How are proto oncogenes converted to oncogenes?
    3 years ago
  • Quartilla
    Which is not a typical mechanism by which a protooncogene is converted to anoncogene?
    3 years ago
  • dora
    How protooncogene convert to oncogene?
    3 years ago
  • christian
    How point mutation converts the proto oncogene to oncogene?
    2 years ago
  • temshe
    How protooncogene convert into oncogene with mechanism?
    2 years ago
  • leea
    Which genes convert proto oncogene into oncogene?
    2 years ago
  • DONALD WILLIAMS
    Which virus is converted to the protooncogenes to oncogenes?
    2 years ago
  • michelino
    How virus convert proto oncogene into oncogene?
    2 years ago
  • mehret
    How normal cellular proto oncogene can be converted to cellular oncogene with diagram?
    2 years ago
  • cora
    What converts proto oncogenes to oncogenes?
    12 months ago
  • rose
    What method is used to convert a protooncogene to an oncogene?
    9 months ago
  • Sofia
    What are the conversion of protooncogene to oncogene?
    8 months ago
  • christine
    What converts a normal cell to an onco cell?
    7 months ago
  • David
    How protooncogene is conerted into the oncogene?
    6 months ago
  • sanelma
    What kind of mutation turns a proto oncogene into an oncogene?
    6 months ago
  • Eleanor
    How a protooncogene can be converted into oncogenes?
    4 months ago
  • tabita
    Can mitogen be converted into an oncogene?
    2 months ago
  • awet
    What changes can convert proboncogene into an oncogene?
    7 days ago
  • TIFFANY
    What can convert proto oncogenes into oncogenes?
    3 days ago

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