Dynamic Development

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The Foundations of Developmental Biology


From Sperm and Egg to Embryo

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Organizing the Multicellular Embryo

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Development and Cancer

Flip sides of the same coin

By Dr. Tracy O'Connor and Dr. Leon Browder

What is cancer?

To put it simply, cancer is inappropriate cellular proliferation.

Once an organism reaches maturity and stops growing, the amount of cell proliferation in its body is restricted to a few specific populations in which continuous turnover is required. Most of the cells in the body remain in a quiescent, non-proliferating state, which corresponds to Go in the cell cycle.  Examples of normally quiescent cell populations are neurons and muscle cells. Examples of non-quiescent cell populations are intestinal epithelial cells and dermal cells. Normally proliferating cell populations are subject to stringent growth control mechanisms.

Cancer is an abnormal state in which uncontrolled proliferation of one or more cell populations interferes with normal biological functioning. The proliferative changes are usually accompanied by other changes in cellular properties, including reversion to a less differentiated, more developmentally primitive state.

The in vitro correlate of cancer is called cellular transformation. Transformed cells generally display several or all of the following properties: spherical morphology, expression of fetal antigens, growth-factor independence, lack of contact inhibition, anchorage-independence, and growth to high density.

Cancer can invade the body to different degrees. In the early stages, the abnormally proliferating cells are usually restricted to the area in which the cancer originated. Progressive changes in the cancer cells may allow them to escape from the primary site (metastasis),  and cause damage to the organism on a larger scale.

Genes involved in cancer

A mutation in any gene which is involved in normal cell growth contol could potentially contribute to the formation of cancer. Generally, cancer is caused not by one mutation, but by multiple mutations, which together allow the cell to escape normal control mechanisms. Although some control mechanisms are common to all cell types, others are tissue-specific. Thus, different genes tend to be implicated in different cancers.

There are two major classes of growth control genes which may be involved in cancer: proto-oncogenes and tumour suppressor genes.

Proto-oncogenes encode proteins which normally activate cellular proliferation. Mutations which increase their activity may contribute to cancer. Examples include survival factors, growth factors, receptors, signal transduction proteins, transcription factors, and positive cell-cycle regulatory proteins. Genes which may contribute to metastasis include ECM proteases, vascularization factors, adhesion molecules, and motility factors.

Tumour-suppressor genes encode proteins which normally suppress cell proliferation. Mutations which decrease their activity may contribute to cancer. Examples include death factors, differentiation factors, receptors, signal transduction proteins, transcription factors, and negative cell-cycle regulators.

An aside on "survival factors", "growth factors" and "differentiation factors"

These factors may be hormones, paracrine factors, or cell surface components. They may be peptides, steroids, or various other types of molecules. They may have different biological functions depending on the circumstances; ie. cell type and developmental stage. For example, the peptide factor EGF promotes proliferation of retinal glial progenitors early in development, but differentiation of retinal glial cells later on (Lillien and Wancio, 1998). How could this happen?

Genes in development and cancer

Cancer has been called a "developmental disorder" (Dean, 1998) because it involves a disruption of the normal developmental program for cells, in terms of both differentiation and proliferation. It follows that some of the molecular players involved in controlling development might be implicated in causing cancer.

We have previously discussed the roles of cadherin and beta-catenin in embryological development of both Xenopus and Drosophila. Humans also express these proteins, and they have been implicated in the formation of basal cell carcinoma. Mutations which result in activation of beta-catenin are found in carcinoma tumors, and over-expression of beta-catenin can cause epithelial cells to become transformed (Orford et al, 1999). A gene which is often mutated in colon cancers, APC, is a tumour-suppressor gene. This gene normally encodes a protein which down-regulates beta-catenin. Other members of the Wnt signalling pathway have also been implicated in cancers, and Wnt itself is a proto-oncogene.

Mutations in the human version of the patched gene, which is a segment polarity gene in Drosophila, cause an inherited form of basal cell carcinoma. Normally, hedgehog binds to the patched protein, which is associated with the smoothened protein. Binding of hedgehog to patched releases the inhibitory effect of patched on smoothened, and results in signal transduction, and expression of the wingless/Wnt gene. If patched is mutated so that it doesn't inhibit smoothened, then smoothened is constitutively activated, and the signal transduction pathway is constantly turned on.

Mutations in the gene bcl-2 often occur in prostate cancers. Mutational over-expression of this survival factor reduces the level of apoptosis in the prostate cell population. This makes the tissue more susceptible to cancer.

Inactivation of the tumour suppressor gene RB causes retinoblastoma, a congenital retinal tumour which often occurs in childhood.  Retinoblastoma is one of the few tumours which can be caused by homologous inactivation of just one gene. Generally, a child is born with a susceptibility to retinoblastoma by inheriting one mutated allele. If the other allele becomes damaged in one or a few cells, so that no active RB protein is made, those cells will be able to proliferate unchecked, and a tumour can develop.


Many of the genes involved in embryogenesis are important for control of cell proliferation and differentiation. Mutations in these genes may contribute to the progression of cancer later in the life of the organism. Thus, research into the molecular mechanisms involved in development is important not only for understanding embryogenesis, but also for understanding, and managing, cancer.

For more information on cell cycle control in relation to cancer, see Dr. Richard Carthew's site on Developmental Biology: Cell Growth and Cancer.

Learning Objectives

  • What is G0?
  • What is START?
  • How do growth factors affect the cell cycle? (Give examples)
  • How does the stimulus from a growth factor influence the nucleus?
  • How do mutations in growth factors cause cancer? (Give an example)
  • How do mutations in growth factor receptors cause cancer? (Give an example)
  • How do mutations in signal transduction molecules cause cancer? (Give an example)
  • How do mutations in cell cycle factors cause cancer? (Give an example)
  • Why is cancer a multi-step process?

Digging Deeper

Links to related material

See Dr. Peter Bryant's page at The University of California, Irvine. Dr. Bryant studies tumor suppressor genes and their human homologs.

Moffitt Cancer Center

A potential new therapeutic approach to cancer treatment.

Are angiogenesis blockers the magic bullets?



Adams, J.M., Cory, S. 1998. The bcl-2 family: arbiters of cell survival. Science 281:1322-1326.

Behrens, J. 1998. Cadherins and catenins: role in signal transduction and tumor progression. Cancer Metastasis Review 18(1): 15-30.

Dean, M. 1998. Cancer as a complex developmental disorder - Nineteenth Cornelius P. Rhoads Memorial Lecture. Cancer Research 58: 5633-5636.

Lillien, L., Wancio, D. 1998. Changes in epidermal growth factor receptor expression and competence to generate glia regulate timing and choice of differentiation in the retina. Mol. Cell. Neurosci. 10(5-6): 296-308.

Orford, K., Orford, C.C., Byers, S.W. 1999. Exogenous expression of beta-catenin regulates contact inhibition, anchorage-independent growth, anoikis, and radiation-induced cell cycle arrest. J. Cell. Biol. 146(4): 855-868.

Dynamic Development at a Glance
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Dynamic Development is a Virtual Embryo learning resource

This material may be reproduced for educational purposes only provided credit is given to the original source.
Leon Browder & Laurie Iten (Ed.) Dynamic Development
Last revised Tuesday, July 21, 1998