[Frontiers in Bioscience 18, 474-492, January 1, 2013]

The role of Rhox homeobox factors in tumorigenesis

James A. MacLean II1

1Department of Physiology, Southern Illinois University, School of Medicine, 1135 Lincoln Dr. PO Box 6652, Carbondale, IL 62901, USA.


1. Abstract
2. Introduction
3. Characteristics of the Rhox homeobox cluster
3.1. Organization and evolution of the Rhox genes
3.2. Expression of the Rhox genes in reproductive tissues
4. Aberrant expression the Rhox cluster in cancer
4.1 .Rhox genes are broadly expressed in cancerous cells of diverse tissue origin
4.2 .Potential mechanisms of Rhox gene misregulation
5. Cellular processes governed by RHOX factors
5.1. RHOX factor regulation of proliferation
5.2. RHOX factors govern differentiation events
5.3. RHOX factors promote cell survival
6. RHOX interacting proteins and links to cancer development and progression
6.1 .MEN1
6.2 .CDC37
6.3 .PSAP
6.4 .MDFIC
7. Discussion and future directions
8. Acknowledgments:
9. References


Homeobox genes encode transcription factors that have well-established roles in embryonic development. We recently discovered the Rhox genes, a new family of homeobox genes, which are selectively expressed in the developing embryo, postnatal and adult gonads, and accessory tissues associated with mammalian reproduction. The largest and best-characterized Rhox cluster is found in mouse. However, all mammals examined to date possess a set of Rhox genes that, while they may vary in number by species, appear relevant to reproduction and are located in the syntenic region of the X chromosome. Rhox5, the founding member of the family, was initially cloned from a screen to identify tumorigenic antigens from T-cell lymphomas, and was later found to be widely expressed in tumors from tissues of diverse origins that do not normally express the Rhox genes. This aberrant upregulation appears to be a general feature of many Rhox genes, but the implications of this misexpression remain largely uninvestigated. In this review, we will discuss the latest findings on the normal and abnormal roles of the Rhox genes and their potential contributions to the formation and progression of tumors.