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MYC overexpression corresponds precisely to morphological changes in luminal cells that are characteristic of PIN.

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posted on 2010-02-25, 00:35 authored by Tsuyoshi Iwata, Denise Schultz, Jessica Hicks, Gretchen K. Hubbard, Laura N. Mutton, Tamara L. Lotan, Carlise Bethel, Matthew T. Lotz, Srinivasan Yegnasubramanian, William G. Nelson, Chi V. Dang, MengMeng Xu, Uzoma Anele, Cheryl M. Koh, Charles J. Bieberich, Angelo M. De Marzo

(A–C). Low power (original magnification 20×) image of an entire lobe of a mouse ventral prostate at four weeks of age from a Lo-MYC mouse. Stains are indicated above images. Sections are not directly adjacent but are within ∼25–40 µM (of each other. Note the highly heterogeneous nature of the staining for MYC and Nkx3.1. (D–F). Medium power (100 ×) view of regions shown in the box in Figure 3A. Regions corresponding to normal appearing epithelium are circled in black, and regions corresponding to PIN lesions are circled in red. Note that regions of PIN are staining positively for MYC and the same regions are staining at a much reduced level for Nkx3.1. Also note small area in panel E that lacks staining for MYC, indicated by the arrow, which has strong positive staining for Nkx3.1 (indicated by the arrow in panel F). (G–I). Higher power image of region of transition between normal epithelium and PIN (the lowermost gland in panels D–F). Here it is clearly evident that cells corresponding to PIN cells, as shown in the H&E section (panel G) are the same cells that are staining strongly positive for MYC, and the same cells that have markedly reduced staining for Nkx3.1. (J) Western blot (left) showing reduced Nkx3.1 protein in a Lo-MYC mouse ventral prostate with PIN, as compared to an FVB wild-type mouse at the same age (six months). Northern blot (right) showing reduced Nkx3.1 mRNA in a Lo-MYC mouse ventral prostate with PIN as compared to an FVB mouse at the same age (9 weeks). Top right shows MYC mRNA is highly elevated in another Lo-MYC mouse ventral prostate as compared to a matched FVB wild-type (9 weeks).