Abstract C5: Role of ID4 in the development of prostate in mouse

Abstract

Abstract Introduction: The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key players in a wide array of developmental processes. Studies in mice have convincingly demonstrated that HLH proteins are intimately involved in developmental events such as cellular differentiation and proliferation. The Id1, Id2, Id3 and Id4 gene products are closely related in their HLH regions and show similar affinities for the various E proteins but differ in their expression patterns. The function of Id proteins has recently been addressed by using a gene targeting approach in mice. Previous studies showed that Id1 null mutant mice do not exhibit abnormalities whereas reports from Id4−/− mice, found that Id4 is required for normal brain size, and regulates lateral expansion of the proliferative zone in the developing cortex and hippocampus. We have recently shown that Id4 is highly expressed in the normal human prostate, whereas its expression is epigenetically silenced in prostate cancer. However its role in normal prostate development and function is not known. Here, we demonstrate a role of Id4 in prostate development, by immunohistochemical techniques in Id4−/− mice. Experimental procedures: To investigate the precise role of Id4 in cellular proliferation and development, normal H&E staining is performed on wild type and Id4−/− mouse prostate tissue. Expression of Id1, AR (Androgen receptor) and NKX3.1 on wild type and Id4−/− mouse prostate tissue was assessed by Immunohistochemistry. Results: There was no change in expression of Id1 in wild type and Id4−/− mouse prostate. Androgen receptor and NKX3.1 expression in wild type mouse was mostly nuclear but there is no expression was observed in Id4−/− mouse prostate tissue. H&E staining of wild type and Id4−/− mouse prostate indicated a significant difference in the cellular morphology of Id4−/− mouse prostate tissue as compared to the wild type mouse prostate. In addition to cellular morphological changes, the size of androgen dependent reproductive tract organs such as seminal vesicle and prostate were significantly smaller in Id4−/− as compared to heterozygous and wild type mouse. Conclusions: These results suggest a severe defect in androgen response pathway and support the role of Id4 in prostate development. Difference in the size of seminal vesicles and prostate in Id4−/− mouse shows the physiological role of Id4 in androgen target organs. Size difference could be due to lack of translocation of AR to nuclei however exact molecular mechanism remains to be investigated. Acknowledgement: The research was supported by NIH/NCI-RO1CA128914 and in part by NIH/NCRR/RCMI G12RR03062. Citation Format: Pankaj Sharma, Peri Nagappan, Mark A. Israel, Jaideep Chaudhary. Role of ID4 in the development of prostate in mouse [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C5.