Expression of Fox Head Protein 1 in Human Eutopic Endometrium and Endometriosis

The objective of this study is to examine the localization and expression of FOXP1 in human endometrium during the menstrual cycle and in endometriotic lesions and endometrial adenocarcinoma. FOXP1 protein expression was analyzed by immunohistochemistry and Western blot. FOXP1 expression was significantly different between glandular epithelial and stromal nuclei and cytoplasm in both endometrial functionalis and basalis. FOXP1 immunostaining was significantly reduced in the early secretory stage in comparison to the mid proliferative stage in the functionalis and the early proliferative stage in the basalis. FOXP1 expression was found in endometriotic lesions but not in endometrial adenocarcinoma. Multiple protein bands of FOXP1 were identified, and their presence varied considerably among patients. Protein expression levels were significantly higher in the mid and late secretory stages in comparison to early proliferative and early secretory stages. FOXP1 protein is present in human endometrium with evidence of dependent changes in expression. Similar content being viewed by others

Dockery P. The fine structure of the mature human endometrium. In: Glasser SR, Aplin JD, Giudice LC, Tabibzadeh S, eds. The Endometrium. London, PA: Taylor & Francis; 2002:21–38. Smith SK The menstrual cycle. In: Glasser SR, Aplin JD, Giudice LC, Tabibzadeh S, eds. The Endometrium. London, PA: Taylor & Francis; 2002:73–85. Graham JD, Clarke CL Physiological action of progesterone in target tissues. Endocr Rev. 1997;18:502–519. Hopwood D., Levison DA Atrophy and apoptosis in the cyclical human endometrium. J Pathol. 1976;119:159–166. Kokawa K., Shikone T., Nakano R. Apoptosis in the human uterine endometrium during the menstrual cycle. J Clin Endocrinol Metab. 1996;81:4144–4147. Okulicz WC Regeneration. In: Glasser SR, Aplin JD, Giudice LC, Tabibzadeh S, eds. The Endometrium. London, PA: Taylor & Francis; 2002:110–120. Carlsson P., Mahlapuu M. Forkhead transcription factors: key players in development and metabolism. Dev Biol. 2002;250:1–23. Katoh M., Katoh M. Human FOX gene family. Int J Oncol. 2004;25:1495–1500. Banham AH, Beasley N., Campo E., et al. The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res. 2001;61:8820–8829. Wang B., Lin D., Li C., Tucker P. Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors. J Biol Chem. 2003;278:24259–24268. Shu W., Yang H., Zhang L., Lu MM, Morrisey EE Characterization of a new subfamily of winged-helix/ forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors. J Biol Chem. 2001;276:27488–27497. Shu W., Lu MM, Zhang Y., et al. Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development. 2007;134:1991–2000. Ferland RJ, Cherry TJ, Preware PO, Morrisey EE, Walsh CA Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J Comp Neurol. 2003;460: 266–279. Hu H., Wang B., Borde M., et al. Foxp1 is an essential transcriptional regulator of B cell development. Nat Immunol. 2006;7:819–826. Wang B., Weidenfeld J., Lu MM, et al. Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development. 2004;131: 4477–4487. Giatromanolaki A., Koukourakis MI, Sivridis E., et al. Loss of expression and nuclear/cytoplasmic localization of the FOXP1 forkhead transcription factor are common events in early endometrial cancer: relationship with estrogen receptors and HIF-1alpha expression. Mod Pathol. 2006;19:9–16. Fox SB, Brown P., Han C., et al. Expression of the forkhead transcription factor FOXP1 is associated with estrogen receptor α and improved survival in primary human breast carcinomas. Clin Cancer Res. 2004;10:3521–3527. Haralambieva E., Adam P., Ventura R., et al. Genetic rearrangement of FOXP1 is predominantly detected in a subset of diffuse large B-cell lymphomas with extranodal presentation. Leukemia. 2006;20:1300–1303. Shimizu K., Kato A., Hinotsume D., et al. Reduced expressions of Foxp1 and Rassf1a genes in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in rats. Cancer Lett. 2006;236:186–190. Banham A., Brown P., Baldry C., Ott G. Expression of the FOXP1 transcription factor is stronger in activated B-like diffuse large B cell lymphomas. J Clin Pathol. 2002;55(suppl 1):28. Barrans SL, Fenton JA, Banham A., Owen RG, Jack AS Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004;104:2933–2935. Wolf I., Bose S., Williamson EA, et al. FOXA1: growth inhibitor and a favorable prognostic factor in human breast cancer. Int J Cancer. 2007;120:1013–1022. Sagaert X., de Paepe P., Libbrecht L., et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:2490–2497. Kitawaki J., Kado N., Ishihara H., et al. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83:149–155. Gurates B., Bulun SE Endometriosis: the ultimate hormonal disease. Semin Reprod Med. 2003;21:125–134. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Am J Obstet Gynecol. 1975;122:262–263. Man TK, Li Y., Dang TA, et al. Optimising the use of TRIzolextracted proteins in surface enhanced laser desorption/ ionization (SELDI) analysis. Proteome Sci. 2006;4:3. Thierry-Mieg D., Thierry-Mieg J. AceView: a comprehensive cDNA-supported gene and transcripts annotation. Genome Biol. 2006;7(suppl 1):S12.1–S12.14. Li C., Tucker PW DNA-binding properties and secondary structural model of the hepatocyte nuclear factor 3/fork head domain. Proc Natl Acad Sci U S A. 1993;90:11583–11587. Jones MH, Nakamura Y. Deletion mapping of chromosome 3p in female genital tract malignancies using microsatellite polymorphisms. Oncogene. 1992;7:1631–1634. Fujino T., Risinger JI, Collins NK, et al. Allelotype of endometrial carcinoma. Cancer Res. 1994;54:4294–4298. Bulun SE, Yang S., Fang Z., et al. Estrogen production and metabolism in endometriosis. Ann N Y Acad Sci. 2002;955: 75–85. Author information Authors and Affiliations Corresponding author Additional information Ms Fu was supported by the Australian Postgraduate Award. Dr Girling’s salary was provided by NH & MRC grant 384195. Dr Rogers’s salary was provided by NH & MRC fellowship grant 143805.We thank Leonie Cann and Dr Anna Ponnampalam for their technical assistance with immunohistochemistry and Western blotting, respectively.We also thank clinical research nurses Nancy Taylor, Nicki Sam, and Pam Mamers and the surgeons for tissue collection and the patients of Monash Medical Centre for their participation. Rights and permissions About this article Cite this article Fu, L., Girling, J.E. & Rogers, P.A.W. Expression of Fox Head Protein 1 in Human Eutopic Endometrium and Endometriosis. Reprod. Sci. 15, 243–252 (2008). https://doi.org/10.1177/1933719107312626 Published: Issue date: DOI: https://doi.org/10.1177/1933719107312626