The Role of Rhox Homeobox Factors in Tumorigenesis

Overview

Journal Front Biosci (Landmark Ed)

Specialty Biology

Date 2013 Jan 2

PMID 23276937

Citations 8

Authors

James A MacLean 2nd

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

The MexTAg collaborative cross: host genetics affects asbestos related disease latency, but has little influence once tumours develop.

Fisher S, Patrick K, Hoang T, Marcq E, Behrouzfar K, Young S Front Toxicol. 2024; 6:1373003.

PMID: 38694815 PMC: 11061428. DOI: 10.3389/ftox.2024.1373003.

Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.

Diaz-Villegas V, Pichardo-Macias L, Juarez-Mendez S, Ignacio-Mejia I, Cardenas-Rodriguez N, Antonio Vargas-Hernandez M Int J Mol Sci. 2024; 25(3).

PMID: 38338984 PMC: 10855401. DOI: 10.3390/ijms25031690.

Mammal Reproductive Homeobox (Rhox) Genes: An Update of Their Involvement in Reproduction and Development.

Le Beulze M, Daubech C, Balde-Camara A, Ghieh F, Vialard F Genes (Basel). 2023; 14(9).

PMID: 37761825 PMC: 10531175. DOI: 10.3390/genes14091685.

Rhox8 homeobox gene ablation leads to rete testis abnormality and male subfertility in mice†.

Oh Y, Kasu M, Bottoms C, Douglas J, Sekulovski N, Hayashi K Biol Reprod. 2023; 109(4):520-532.

PMID: 37471646 PMC: 10577278. DOI: 10.1093/biolre/ioad077.

Mouse Spermatogenesis Requires Classical and Nonclassical Testosterone Signaling.

Toocheck C, Clister T, Shupe J, Crum C, Ravindranathan P, Lee T Biol Reprod. 2015; 94(1):11.

PMID: 26607719 PMC: 4809556. DOI: 10.1095/biolreprod.115.132068.

References

Geyer C, Eddy E . Identification and characterization of Rhox13, a novel X-linked mouse homeobox gene. Gene. 2008; 423(2):194-200. PMC: 2614869. DOI: 10.1016/j.gene.2008.06.031. View

Fleenor D, Freemark M . Prolactin induction of insulin gene transcription: roles of glucose and signal transducer and activator of transcription 5. Endocrinology. 2001; 142(7):2805-10. DOI: 10.1210/endo.142.7.8267. View

Wayne C, MacLean J, Cornwall G, Wilkinson M . Two novel human X-linked homeobox genes, hPEPP1 and hPEPP2, selectively expressed in the testis. Gene. 2002; 301(1-2):1-11. DOI: 10.1016/s0378-1119(02)01087-9. View

Li Q, Bartlett D, Gorry M, OMalley M, Guo Z . Three epigenetic drugs up-regulate homeobox gene Rhox5 in cancer cells through overlapping and distinct molecular mechanisms. Mol Pharmacol. 2009; 76(5):1072-81. DOI: 10.1124/mol.109.056291. View

Sutton K, Wilkinson M . Rapid evolution of a homeodomain: evidence for positive selection. J Mol Evol. 1998; 45(6):579-88. DOI: 10.1007/pl00006262. View

Hofmann O, Caballero O, Stevenson B, Chen Y, Cohen T, Chua R . Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci U S A. 2008; 105(51):20422-7. PMC: 2603434. DOI: 10.1073/pnas.0810777105. View

Fan Y, Nikitina T, Zhao J, Fleury T, Bhattacharyya R, Bouhassira E . Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell. 2005; 123(7):1199-212. DOI: 10.1016/j.cell.2005.10.028. View

Spitz F, Duboule D . Developmental biology: reproduction in clusters. Nature. 2005; 434(7034):715-6. DOI: 10.1038/434715a. View

Chun J, Han Y, Ahn K . Psx homeobox gene is X-linked and specifically expressed in trophoblast cells of mouse placenta. Dev Dyn. 1999; 216(3):257-66. DOI: 10.1002/(SICI)1097-0177(199911)216:3<257::AID-DVDY4>3.0.CO;2-0. View

10.

De Gendt K, Swinnen J, Saunders P, Schoonjans L, Dewerchin M, Devos A . A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci U S A. 2004; 101(5):1327-32. PMC: 337052. DOI: 10.1073/pnas.0308114100. View

11.

MacLean 2nd J, Hayashi K, Turner T, Wilkinson M . The Rhox5 homeobox gene regulates the region-specific expression of its paralogs in the rodent epididymis. Biol Reprod. 2012; 86(6):189. PMC: 3386150. DOI: 10.1095/biolreprod.112.099184. View

12.

Nakajima J, Ishikawa S, Hamada J, Yanagihara M, Koike T, Hatakeyama M . Anti-tumor activity of ESX1 on cancer cells harboring oncogenic K-ras mutation. Biochem Biophys Res Commun. 2008; 370(1):189-94. DOI: 10.1016/j.bbrc.2008.03.062. View

13.

Niu A, Wang Y, Zhang H, Liao C, Wang J, Zhang R . Rapid evolution and copy number variation of primate RHOXF2, an X-linked homeobox gene involved in male reproduction and possibly brain function. BMC Evol Biol. 2011; 11:298. PMC: 3214919. DOI: 10.1186/1471-2148-11-298. View

14.

Sutton K, Maiti S, Tribley W, Lindsey J, Meistrich M, Bucana C . Androgen regulation of the Pem homeodomain gene in mice and rat Sertoli and epididymal cells. J Androl. 1998; 19(1):21-30. View

15.

MacLean 2nd J, Rao M, Doyle K, Richards J, Wilkinson M . Regulation of the Rhox5 homeobox gene in primary granulosa cells: preovulatory expression and dependence on SP1/SP3 and GABP. Biol Reprod. 2005; 73(6):1126-34. DOI: 10.1095/biolreprod.105.042747. View

16.

MacLean 2nd J, Wilkinson M . Gene regulation in spermatogenesis. Curr Top Dev Biol. 2005; 71:131-97. DOI: 10.1016/S0070-2153(05)71005-X. View

17.

Geyer C, Saba R, Kato Y, Anderson A, Chappell V, Saga Y . Rhox13 is translated in premeiotic germ cells in male and female mice and is regulated by NANOS2 in the male. Biol Reprod. 2011; 86(4):127. PMC: 3338663. DOI: 10.1095/biolreprod.111.094938. View

18.

Bhardwaj A, Rao M, Kaur R, Buttigieg M, Wilkinson M . GATA factors and androgen receptor collaborate to transcriptionally activate the Rhox5 homeobox gene in Sertoli cells. Mol Cell Biol. 2008; 28(7):2138-53. PMC: 2268436. DOI: 10.1128/MCB.01170-07. View

19.

Shibata-Minoshima F, Oki T, Doki N, Nakahara F, Kageyama S, Kitaura J . Identification of RHOXF2 (PEPP2) as a cancer-promoting gene by expression cloning. Int J Oncol. 2011; 40(1):93-8. DOI: 10.3892/ijo.2011.1173. View

20.

Pitman J, Lin T, Kleeman J, Erickson G, Macleod C . Normal reproductive and macrophage function in Pem homeobox gene-deficient mice. Dev Biol. 1998; 202(2):196-214. DOI: 10.1006/dbio.1998.8978. View