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  • Review Article
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A PANorama of PAX genes in cancer and development

Nature Reviews Cancer volume 6, pages 52–62 (2006)Cite this article

Key Points

  • An emerging role for several paired box (Pax) genes during development is the prevention of terminal differentiation and maintenance of a progenitor cell state, while also inducing cell-lineage commitment.

  • The involvement of tumour-associated Pax gene expression in promoting cell proliferation and survival is consistent with in vitro observations of tumour cell death induced by Pax-gene knockdown.

  • Five Pax genes, representing subgroups II (PAX2, PAX5 and PAX8) and III (PAX3 and PAX7) of the four Pax family subgroups, are often expressed in a wide range of cancer types.

  • Rearrangements of four of these Pax genes, PAX3, PAX5, PAX7 and PAX8, are associated with characteristic chromosomal translocations that occur in specific tumours.

  • Pax genes in subgroups II and III confer cell motility, cell survival and self-sufficiency in growth signals, which are characteristics that favour tumour progression. Conversely, Pax genes in subgroups I (PAX1 and PAX9) and IV (PAX4 and PAX6) are either less often involved in cancer or their expression is indicative of favourable prognosis, as observed for PAX6 and PAX9.

  • The structural basis of the four subgroups is proposed to explain why Pax genes in subgroups II and III, which contain an octapeptide region and at least a partial homeodomain, are associated with more aggressive cancers, and why the members of subgroups I and IV, possessing only one of these domains, are linked to a favourable outcome.

Abstract

Populations of self-renewing cells that arise during normal embryonic development harbour the potential for rapid proliferation, migration or transdifferentiation and, therefore, tumour generation. So, control mechanisms are essential to prevent rapidly expanding populations from malignant growth. Transcription factors have crucial roles in ensuring establishment of such regulation, with the Pax gene family prominent amongst these. This review examines the role of Pax family members during embryogenesis, and their contribution to tumorigenesis when subverted.

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Figure 1: Cancer contribution of Pax family member subgroups.
Figure 2: Characteristics conferred by Pax genes that are favourable for tumour progression.
Figure 3: Pax control of differentiation.

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Acknowledgements

The authors acknowledge research fellowship support from the Health Research Council of New Zealand.

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Authors and Affiliations

  1. Department of Pathology, University of Otago, PO Box 913, Dunedin, 9001, New Zealand

    Ewan J. D. Robson, Shu-Jie He & Michael R. Eccles

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Correspondence to Michael R. Eccles.

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Supplementary tables S1 and S2 (PDF 368 kb)

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DATABASES

National Cancer Institute

breast cancer

Ewing sarcoma

Kaposi sarcoma

kidney cancer

leukaemias

melanomas

neuroblastomas

non-Hodgkin lymphoma

ovarian cancer

prostate cancer

rhabdomyosarcoma

Wilms tumour

OMIM

papillorenal syndrome

FURTHER INFORMATION

A listing of cancer gene databases

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cancer Genome Anatomy Project (CGAP) gene finder

Human PAX2 Allelic Variant Database

Pax factors — regulatory targets and integration in the TRANSFAC database

Pax in molecular development, University of South Wales Embryology

PAX3 on the Cancer Genetics Web

Glossary

Gleason score

Areas within prostate cancers are graded from one to five to indicate the level of differentiation, five reflecting poorest differentiation. To calculate the Gleason score, the grades given to the most and second most common patterns observed in a tumour are summed, giving a number between two and ten, ten indicating poorest differentiation.

Aniridia

Congenital absence of the iris.

Foveal dysplasia

Abnormal development of the fovea, a pit in the retina.

Sclerotome

The part of the embryogenic segmented mesoderm from which all skeletal tissue arises.

Ultimobranchial body

A diverticulum derived from the third and fourth pharangeal pouches in the developing embryo. The ultimobranchial body fuses with the thyroid gland and gives rise to parafollicular cells.

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Robson, E., He, SJ. & Eccles, M. A PANorama of PAX genes in cancer and development. Nat Rev Cancer 6, 52–62 (2006). https://doi.org/10.1038/nrc1778

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