Abstract 1817: Expression of the Kaiso-binding partner Znf131 negatively correlates with cell proliferation in murine intestinal and human breast tumor tissues.

Znf131 is a relatively uncharacterized member of the POZ-ZF family of transcription factors with suspected roles in both vertebrate development and carcinogenesis. Previous studies from our lab identified Znf131 as a specific binding partner of another POZ-ZF protein, Kaiso, which has been implicated as a regulator of the canonical Wnt signaling pathway. Our lab successfully generated an intestinal-specific Kaiso overexpressing (Kaiso Tg/+ ) mouse model, which was found to exhibit enlarged crypts and mild hyperplasia in the small intestine. Several lines of evidence implicate Znf131 in cell proliferation, but whether Znf131 expression increases or decreases cell proliferation has yet to be elucidated. To determine whether Znf131 expression correlates with increased proliferation in hyperplastic Kaiso Tg/+ crypts, the expression and localization of Znf131 was correlated with the proliferation marker Ki-67 in Kaiso Tg/+ and wildtype (WT) mouse intestinal tissues. Znf131 nuclear expression was localized to the Paneth cell region of the crypts in both the Kaiso Tg/+ and WT small intestinal tissues, but decreased Znf131 expression was observed in the Kaiso Tg/+ model. Intriguingly, Ki-67 was localized to the progenitor cell region of the crypts and was excluded from Znf131-positive nuclei. In contrast to our hypothesis, these results suggest that Znf131 negatively correlates with cell proliferation. Since Znf131 has also been implicated as a regulator of ERα, we repeated these experiments using human breast tumor tissues to determine whether the observed results were tissue specific. We detected decreased nuclear expression of Znf131 in breast tumor tissues compared to matched normal tissues, and we observed a negative correlation between the nuclear expression of Znf131 and the histologic grade and stage of the tumor. Collectively, our results from both murine intestinal and human breast tumor tissues suggest a negative correlation between Znf131 nuclear expression and cell proliferation and raise the possibility that Znf131 may act as a tumor suppressor. Citation Format: Joseph Longo, Shaiya Robinson, Roopali Chaudhary, Juliet M. Daniel. Expression of the Kaiso-binding partner Znf131 negatively correlates with cell proliferation in murine intestinal and human breast tumor tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1817. doi:10.1158/1538-7445.AM2013-1817