Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Research

Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN

Authors: Pankaj Sharma, Ashley Evans Knowell, Swathi Chinaranagari, Shravan Komaragiri, Peri Nagappan, Divya Patel, Mathew C Havrda, Jaideep Chaudhary

Published in: Molecular Cancer | Issue 1/2013

Login to get access

Abstract

Background

Inhibitor of differentiation 4 (Id4), a member of the helix-loop-helix family of transcriptional regulators has emerged as a tumor suppressor in prostate cancer. Id4 is expressed in the normal prostate where its expression is also regulated by androgens. In this study we investigated the effect of loss of Id4 (Id4-/-) on adult prostate morphology.

Methods

Histological analysis was performed on prostates from 6-8 weeks old Id4-/-, Id4+/- and Id4+/+ mice. Expression of Id1, Sox9, Myc, androgen receptor, Akt, p-Akt, Pten and Nkx3.1 was investigated by immunohistochemistry. Androgen receptor binding on NKX3.1 promoter was studied by chromatin immuno-precipitation. Id4 was either over-expressed or silenced in prostate cancer cell lines DU145 and LNCaP respectively followed by analysis of PTEN, NKX3.1 and Sox9 expression.

Results

Id4-/- mice had smaller prostates with fewer tubules, smaller tubule diameters and subtle mPIN like lesions. Levels of androgen receptor were similar between wild type and Id4-/- prostate. Decreased NKX3.1 expression was in part due to decreased androgen receptor binding on NKX3.1 promoter in Id4-/- mice. The increase in the expression of Myc, Sox9, Id1, Ki67 and decrease in the expression of PTEN, Akt and phospho-AKT was associated with subtle mPIN like lesions in Id4-/- prostates. Finally, prostate cancer cell line models in which Id4 was either silenced or over-expressed confirmed that Id4 regulates NKX3.1, Sox9 and PTEN.

Conclusions

Our results suggest that loss of Id4 attenuates normal prostate development and promotes hyperplasia/dysplasia with subtle mPIN like lesions characterized by gain of Myc and Id1 and loss of Nkx3.1 and Pten expression. One of the mechanisms by which Id4 may regulate normal prostate development is through regulating androgen receptor binding to respective response elements such as those on NKX3.1 promoter. In spite of these complex alterations, large neoplastic lesions in Id4-/- prostates were not observed suggesting the possibility of mechanisms/pathways such as loss of Akt that could restrain the formation of significant pre-cancerous lesions.
Appendix
Available only for authorised users
Literature
1.
Ruzinova MB, Benezra R: Id proteins in development, cell cycle and cancer. Trends Cell Biol. 2003, 13: 410-418. 10.1016/S0962-8924(03)00147-8CrossRefPubMed
2.
Coppe JP, Smith AP, Desprez PY: Id proteins in epithelial cells. Exp Cell Res. 2003, 285: 131-145. 10.1016/S0014-4827(03)00014-4CrossRefPubMed
3.
Norton JD, Deed RW, Craggs G, Sablitzky F: Id helix-loop-helix proteins in cell growth and differentiation. Trends Cell Biol. 1998, 8: 58-65.PubMed
4.
de Candia P, Benezra R, Solit DB: A role for Id proteins in mammary gland physiology and tumorigenesis. Adv Cancer Res. 2004, 92: 81-94.CrossRefPubMed
5.
Sakata-Goto T, Takahashi K, Kiso H, Huang B, Tsukamoto H, Takemoto M, Hayashi T, Sugai M, Nakamura T, Yokota Y: Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis. Bone. 2012, 50: 69-78. 10.1016/j.bone.2011.09.049CrossRefPubMed
6.
Li H, Ji M, Klarmann KD, Keller JR: Repression of Id2 expression by Gfi-1 is required for B-cell and myeloid development. Blood. 2010, 116: 1060-1069. 10.1182/blood-2009-11-255075PubMedCentralCrossRefPubMed
7.
Jongbloed MR, Vicente-Steijn R, Douglas YL, Wisse LJ, Mori K, Yokota Y, Bartelings MM, Schalij MJ, Mahtab EA, Poelmann RE, Gittenberger-De Groot AC: Expression of Id2 in the second heart field and cardiac defects in Id2 knock-out mice. Dev Dyn. 2011, 240: 2561-2577. 10.1002/dvdy.22762CrossRefPubMed
8.
Norton JD: ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci. 2000, 113 (Pt 22): 3897-3905.PubMed
9.
Li H, Dai M, Zhuang Y: A T cell intrinsic role of Id3 in a mouse model for primary Sjogren’s syndrome. Immunity. 2004, 21: 551-560. 10.1016/j.immuni.2004.08.013CrossRefPubMed
10.
Pan L, Sato S, Frederick JP, Sun XH, Zhuang Y: Impaired immune responses and B-cell proliferation in mice lacking the Id3 gene. Mol Cell Biol. 1999, 19: 5969-5980.PubMedCentralCrossRefPubMed
11.
Ueda-Hayakawa I, Mahlios J, Zhuang Y: Id3 restricts the developmental potential of gamma delta lineage during thymopoiesis. J Immunol. 2009, 182: 5306-5316. 10.4049/jimmunol.0804249PubMedCentralCrossRefPubMed
12.
Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R: Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature. 1999, 401: 670-677. 10.1038/44334CrossRefPubMed
13.
Yun K, Mantani A, Garel S, Rubenstein J, Israel MA: Id4 regulates neural progenitor proliferation and differentiation in vivo. Development. 2004, 131: 5441-5448. 10.1242/dev.01430CrossRefPubMed
14.
Dong J, Huang S, Caikovski M, Ji S, McGrath A, Custorio MG, Creighton CJ, Maliakkal P, Bogoslovskaia E, Du Z: ID4 regulates mammary gland development by suppressing p38MAPK activity. Development. 2011, 138: 5247-5256. 10.1242/dev.069203PubMedCentralCrossRefPubMed
15.
Oatley MJ, Kaucher AV, Racicot KE, Oatley JM: Inhibitor of DNA binding 4 is expressed selectively by single spermatogonia in the male germline and regulates the self-renewal of spermatogonial stem cells in mice. Biol Reprod. 2011, 85: 347-356. 10.1095/biolreprod.111.091330PubMedCentralCrossRefPubMed
16.
Tokuzawa Y, Yagi K, Yamashita Y, Nakachi Y, Nikaido I, Bono H, Ninomiya Y, Kanesaki-Yatsuka Y, Akita M, Motegi H: Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation. PLoS Genet. 2010, 6: e1001019- 10.1371/journal.pgen.1001019PubMedCentralCrossRefPubMed
17.
Murad JM, Place CS, Ran C, Hekmatyar SK, Watson NP, Kauppinen RA, Israel MA: Inhibitor of DNA binding 4 (ID4) regulation of adipocyte differentiation and adipose tissue formation in mice. J Biol Chem. 2010, 285: 24164-24173. 10.1074/jbc.M110.128744PubMedCentralCrossRefPubMed
18.
19.
Yu L, Liu C, Vandeusen J, Becknell B, Dai Z, Wu YZ, Raval A, Liu TH, Ding W, Mao C: Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia. Nat Genet. 2005, 37: 265-274. 10.1038/ng1521CrossRefPubMed
20.
Umetani N, Mori T, Koyanagi K, Shinozaki M, Kim J, Giuliano AE, Hoon DS: Aberrant hypermethylation of ID4 gene promoter region increases risk of lymph node metastasis in T1 breast cancer. Oncogene. 2005, 24: 4721-4727. 10.1038/sj.onc.1208538CrossRefPubMed
21.
Noetzel E, Veeck J, Niederacher D, Galm O, Horn F, Hartmann A, Knuchel R, Dahl E: Promoter methylation-associated loss of ID4 expression is a marker of tumour recurrence in human breast cancer. BMC Cancer. 2008, 8: 154- 10.1186/1471-2407-8-154PubMedCentralCrossRefPubMed
22.
Umetani N, Takeuchi H, Fujimoto A, Shinozaki M, Bilchik AJ, Hoon DS: Epigenetic inactivation of ID4 in colorectal carcinomas correlates with poor differentiation and unfavorable prognosis. Clin Cancer Res. 2004, 10: 7475-7483. 10.1158/1078-0432.CCR-04-0689CrossRefPubMed
23.
Chen SS, Claus R, Lucas DM, Yu L, Qian J, Ruppert AS, West DA, Williams KE, Johnson AJ, Sablitzky F: Silencing of the inhibitor of DNA binding protein 4 (ID4) contributes to the pathogenesis of mouse and human CLL. Blood. 2011, 117: 862-871. 10.1182/blood-2010-05-284638PubMedCentralCrossRefPubMed
24.
Chan AS, Tsui WY, Chen X, Chu KM, Chan TL, Li R, So S, Yuen ST, Leung SY: Downregulation of ID4 by promoter hypermethylation in gastric adenocarcinoma. Oncogene. 2003, 22: 6946-6953. 10.1038/sj.onc.1206799CrossRefPubMed
25.
Bellido M, Aventin A, Lasa A, Estivill C, Carnicer MJ, Pons C, Matias-Guiu X, Bordes R, Baiget M, Sierra J, Nomdedeu JF: Id4 is deregulated by a t(6;14)(p22;q32) chromosomal translocation in a B-cell lineage acute lymphoblastic leukemia. Haematologica. 2003, 88: 994-1001.PubMed
26.
Russell LJ, Akasaka T, Majid A, Sugimoto KJ, Loraine Karran E, Nagel I, Harder L, Claviez A, Gesk S, Moorman AV: t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood. 2008, 111: 387-391. 10.1182/blood-2007-07-092015CrossRefPubMed
27.
Wu Q, Hoffmann MJ, Hartmann FH, Schulz WA: Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer. Mol Cancer. 2005, 4: 16- 10.1186/1476-4598-4-16PubMedCentralCrossRefPubMed
28.
Shan L, Yu M, Qiu C, Snyderwine EG: Id4 regulates mammary epithelial cell growth and differentiation and is overexpressed in rat mammary gland carcinomas. Am J Pathol. 2003, 163: 2495-2502. 10.1016/S0002-9440(10)63604-8PubMedCentralCrossRefPubMed
29.
Sharma P, Chinaranagari S, Patel D, Carey J, Chaudhary J: Epigenetic inactivation of inhibitor of differentiation 4 (Id4) correlates with prostate cancer. Cancer Med. 2012, 1 (2): 176-186. 10.1002/cam4.16PubMedCentralCrossRefPubMed
30.
Vinarskaja A, Goering W, Ingenwerth M, Schulz WA: ID4 is frequently downregulated and partially hypermethylated in prostate cancer. World J Urol. 2012, 30: 319-325. 10.1007/s00345-011-0750-8CrossRefPubMed
31.
Yu X, Xu X, Han B, Zhou R: Inhibitor of DNA binding-1 overexpression in prostate cancer: relevance to tumor differentiation. Pathol Oncol Res. 2009, 15: 91-96. 10.1007/s12253-008-9096-yCrossRefPubMed
32.
Coppe JP, Itahana Y, Moore DH, Bennington JL, Desprez PY: Id-1 and Id-2 proteins as molecular markers for human prostate cancer progression. Clin Cancer Res. 2004, 10: 2044-2051. 10.1158/1078-0432.CCR-03-0933CrossRefPubMed
33.
Sharma P, Patel D, Chaudhary J: Id1 and Id3 expression is associated with increasing grade of prostate cancer: Id3 preferentially regulates CDKN1B. Cancer Med. 2012, 1: 187-197. 10.1002/cam4.19PubMedCentralCrossRefPubMed
34.
Asirvatham AJ, Schmidt MA, Chaudhary J: Non-redundant inhibitor of differentiation (Id) gene expression and function in human prostate epithelial cells. Prostate. 2006, 66: 921-935. 10.1002/pros.20366CrossRefPubMed
35.
Carey JP, Asirvatham AJ, Galm O, Ghogomu TA, Chaudhary J: Inhibitor of differentiation 4 (Id4) is a potential tumor suppressor in prostate cancer. BMC Cancer. 2009, 9: 173- 10.1186/1471-2407-9-173PubMedCentralCrossRefPubMed
36.
Shappell SB, Thomas GV, Roberts RL, Herbert R, Ittmann MM, Rubin MA, Humphrey PA, Sundberg JP, Rozengurt N, Barrios R: Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee. Cancer Res. 2004, 64: 2270-2305. 10.1158/0008-5472.CAN-03-0946CrossRefPubMed
37.
Gipp J, Gu G, Crylen C, Kasper S, Bushman W: Hedgehog pathway activity in the LADY prostate tumor model. Mol Cancer. 2007, 6: 19- 10.1186/1476-4598-6-19PubMedCentralCrossRefPubMed
38.
Bieberich CJ, Fujita K, He WW, Jay G: Prostate-specific and androgen-dependent expression of a novel homeobox gene. J Biol Chem. 1996, 271: 31779-31782. 10.1074/jbc.271.50.31779CrossRefPubMed
39.
DA Bhatia-Gaur R, Sciavolino PJ, Kim M, Desai N, Young P, Norton CR, Gridley T, Cardiff RD, Cunha GR, Abate-Shen C, Shen MM: Roles for Nkx3.1 in prostate development and cancer. Genes Dev. 1999, 13: 966-977. 10.1101/gad.13.8.966CrossRef
40.
Kojima C, Zhang Y, Zimmer WE: Intronic DNA elements regulate androgen-dependent expression of the murine Nkx3.1 gene. Gene Expr. 2010, 15: 89-102.CrossRefPubMed
41.
Lei Q, Jiao J, Xin L, Chang CJ, Wang S, Gao J, Gleave ME, Witte ON, Liu X, Wu H: NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss. Cancer Cell. 2006, 9: 367-378. 10.1016/j.ccr.2006.03.031CrossRefPubMed
42.
Zheng H, Ying H, Yan H, Kimmelman AC, Hiller DJ, Chen AJ, Perry SR, Tonon G, Chu GC, Ding Z: Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harb Symp Quant Biol. 2008, 73: 427-437. 10.1101/sqb.2008.73.047CrossRefPubMed
43.
Abate-Shen C, Banach-Petrosky WA, Sun X, Economides KD, Desai N, Gregg JP, Borowsky AD, Cardiff RD, Shen MM: Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Cancer Res. 2003, 63: 3886-3890.PubMed
44.
Sollazzo MR, Benassi MS, Magagnoli G, Gamberi G, Molendini L, Ragazzini P, Merli M, Ferrari C, Balladelli A, Picci P: Increased c-myc oncogene expression in Ewing’s sarcoma: correlation with Ki67 proliferation index. Tumori. 1999, 85: 167-173.PubMed
45.
Jung S, Park RH, Kim S, Jeon YJ, Ham DS, Jung MY, Kim SS, Lee YD, Park CH, Suh-Kim H: Id proteins facilitate self-renewal and proliferation of neural stem cells. Stem Cells Dev. 2010, 19: 831-841. 10.1089/scd.2009.0093CrossRefPubMed
46.
Iwata T, Schultz D, Hicks J, Hubbard GK, Mutton LN, Lotan TL, Bethel C, Lotz MT, Yegnasubramanian S, Nelson WG: MYC overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells. PLoS One. 2010, 5: e9427- 10.1371/journal.pone.0009427PubMedCentralCrossRefPubMed
47.
Anderson PD, McKissic SA, Logan M, Roh M, Franco OE, Wang J, Doubinskaia I, van der Meer R, Hayward SW, Eischen CM: Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis. J Clin Invest. 2012, 122: 1907-1919. 10.1172/JCI58540PubMedCentralCrossRefPubMed
48.
Alani RM, Young AZ, Shifflett CB: Id1 regulation of cellular senescence through transcriptional repression of p16/Ink4a. Proc Natl Acad Sci USA. 2001, 98: 7812-7816. 10.1073/pnas.141235398PubMedCentralCrossRefPubMed
49.
Prabhu S, Ignatova A, Park ST, Sun XH: Regulation of the expression of cyclin-dependent kinase inhibitor p21 by E2A and Id proteins. Mol Cell Biol. 1997, 17: 5888-5896.PubMedCentralCrossRefPubMed
50.
Asirvatham AJ, Carey JP, Chaudhary J: ID1-, ID2-, and ID3-regulated gene expression in E2A positive or negative prostate cancer cells. Prostate. 2007, 67: 1411-1420. 10.1002/pros.20633CrossRefPubMed
51.
Thomsen MK, Ambroisine L, Wynn S, Cheah KS, Foster CS, Fisher G, Berney DM, Moller H, Reuter VE, Scardino P: SOX9 elevation in the prostate promotes proliferation and cooperates with PTEN loss to drive tumor formation. Cancer Res. 2010, 70: 979-987. 10.1158/0008-5472.CAN-09-2370PubMedCentralCrossRefPubMed
52.
Thomsen MK, Francis JC, Swain A: The role of Sox9 in prostate development. Differentiation. 2008, 76: 728-735. 10.1111/j.1432-0436.2008.00293.xCrossRefPubMed
53.
Wang H, Leav I, Ibaragi S, Wegner M, Hu GF, Lu ML, Balk SP, Yuan X: SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion. Cancer Res. 2008, 68: 1625-1630. 10.1158/0008-5472.CAN-07-5915CrossRefPubMed
54.
Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997, 275: 1943-1947. 10.1126/science.275.5308.1943CrossRefPubMed
55.
Walters KA, Simanainen U, Handelsman DJ: Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models. Hum Reprod Update. 2010, 16: 543-558. 10.1093/humupd/dmq003CrossRefPubMed
56.
Simanainen U, Allan CM, Lim P, McPherson S, Jimenez M, Zajac JD, Davey RA, Handelsman DJ: Disruption of prostate epithelial androgen receptor impedes prostate lobe-specific growth and function. Endocrinology. 2007, 148: 2264-2272. 10.1210/en.2006-1223CrossRefPubMed
57.
Simanainen U, McNamara K, Gao YR, Handelsman DJ: Androgen sensitivity of prostate epithelium is enhanced by postnatal androgen receptor inactivation. Am J Physiol Endocrinol Metab. 2009, 296: E1335-E1343. 10.1152/ajpendo.00017.2009CrossRefPubMed
58.
Wu CT, Altuwaijri S, Ricke WA, Huang SP, Yeh S, Zhang C, Niu Y, Tsai MY, Chang C: Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor. Proc Natl Acad Sci U S A. 2007, 104: 12679-12684. 10.1073/pnas.0704940104PubMedCentralCrossRefPubMed
59.
Abdulkadir SA: Mechanisms of prostate tumorigenesis: roles for transcription factors Nkx3.1 and Egr1. Ann N Y Acad Sci. 2005, 1059: 33-40. 10.1196/annals.1339.018CrossRefPubMed
60.
Ellwood-Yen K, Graeber TG, Wongvipat J, Iruela-Arispe ML, Zhang J, Matusik R, Thomas GV, Sawyers CL: Myc-driven murine prostate cancer shares molecular features with human prostate tumors. Cancer Cell. 2003, 4: 223-238. 10.1016/S1535-6108(03)00197-1CrossRefPubMed
61.
Sikder HA, Devlin MK, Dunlap S, Ryu B, Alani RM: Id proteins in cell growth and tumorigenesis. Cancer Cell. 2003, 3: 525-530. 10.1016/S1535-6108(03)00141-7CrossRefPubMed
62.
Schmidt M, Asirvatham AJ, Chaudhary J: Inhibitor of differentiation 1 (ID1) promotes cell survival and proliferation of prostate epithelial cells. Cell Mol Biol Lett. 2010, 15: 272-295. 10.2478/s11658-010-0007-3CrossRefPubMed
63.
Asirvatham AJ, Schmidt M, Gao B, Chaudhary J: Androgens regulate the immune/inflammatory response and cell survival pathways in rat ventral prostate epithelial cells. Endocrinology. 2006, 147: 257-271.CrossRefPubMed
64.
Scott CE, Wynn SL, Sesay A, Cruz C, Cheung M, Gomez Gaviro MV, Booth S, Gao B, Cheah KS, Lovell-Badge R, Briscoe J: SOX9 induces and maintains neural stem cells. Nat Neurosci. 2010, 13: 1181-1189. 10.1038/nn.2646CrossRefPubMed
65.
Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, Yang A, Montironi R, McKeon F, Loda M: p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol. 2000, 157: 1769-1775. 10.1016/S0002-9440(10)64814-6PubMedCentralCrossRefPubMed
66.
Blum R, Gupta R, Burger PE, Ontiveros CS, Salm SN, Xiong X, Kamb A, Wesche H, Marshall L, Cutler G: Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. PLoS One. 2009, 4: e5722- 10.1371/journal.pone.0005722PubMedCentralCrossRefPubMed
67.
Chen ML, Xu PZ, Peng XD, Chen WS, Guzman G, Yang X, Di Cristofano A, Pandolfi PP, Hay N: The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. Genes Dev. 2006, 20: 1569-1574. 10.1101/gad.1395006PubMedCentralCrossRefPubMed
68.
Clegg NJ, Couto SS, Wongvipat J, Hieronymus H, Carver BS, Taylor BS, Ellwood-Yen K, Gerald WL, Sander C, Sawyers CL: MYC cooperates with AKT in prostate tumorigenesis and alters sensitivity to mTOR inhibitors. PLoS One. 2011, 6: e17449- 10.1371/journal.pone.0017449PubMedCentralCrossRefPubMed
69.
Chen WS, Xu PZ, Gottlob K, Chen ML, Sokol K, Shiyanova T, Roninson I, Weng W, Suzuki R, Tobe K: Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. 2001, 15: 2203-2208. 10.1101/gad.913901PubMedCentralCrossRefPubMed
70.
Prins GS, Putz O: Molecular signaling pathways that regulate prostate gland development. Differentiation. 2008, 76: 641-659. 10.1111/j.1432-0436.2008.00277.xPubMedCentralCrossRefPubMed
71.
Bedford L, Walker R, Kondo T, van Cruchten I, King ER, Sablitzky F: Id4 is required for the correct timing of neural differentiation. Dev Biol. 2005, 280: 386-395. 10.1016/j.ydbio.2005.02.001CrossRefPubMed
72.
Fanelli M, Amatori S, Barozzi I, Minucci S: Chromatin immunoprecipitation and high-throughput sequencing from paraffin-embedded pathology tissue. Nat Protoc. 2011, 6: 1905-1919. 10.1038/nprot.2011.406CrossRefPubMed
73.
Yoon HG, Wong J: The corepressors silencing mediator of retinoid and thyroid hormone receptor and nuclear receptor corepressor are involved in agonist- and antagonist-regulated transcription by androgen receptor. Mol Endocrinol. 2006, 20: 1048-1060. 10.1210/me.2005-0324CrossRefPubMed
74.
Schneider CA, Rasband WS, Eliceiri KW: NIH Image to ImageJ: 25 years of image analysis. Nat Meth. 2012, 9: 671-675. 10.1038/nmeth.2089. 10.1038/nmeth.2089CrossRef
Metadata
Title
Id4 deficiency attenuates prostate development and promotes PIN-like lesions by regulating androgen receptor activity and expression of NKX3.1 and PTEN
Authors
Pankaj Sharma
Ashley Evans Knowell
Swathi Chinaranagari
Shravan Komaragiri
Peri Nagappan
Divya Patel
Mathew C Havrda
Jaideep Chaudhary
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-67

Other articles of this Issue 1/2013

Molecular Cancer 1/2013 Go to the issue

Research

Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells

Reviewer acknowledgement

Thanking our peer reviewers

Review

Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds

Research

Small molecule antagonist of the bone morphogenetic protein type I receptors suppresses growth and expression of Id1 and Id3 in lung cancer cells expressing Oct4 or nestin

Commentary

Cancer: tilting at windmills?

Research

Quizartinib (AC220) is a potent second generation class III tyrosine kinase inhibitor that displays a distinct inhibition profile against mutant-FLT3, -PDGFRA and -KIT isoforms
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits