14. Wang, TC; Cardiff, RD; Zukerberg, L; Lees, E; Arnold, A; Schmidt, EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature, 1994 Jun 23, 369(6482):669-71. (ABSTRACT)(ILLUSTRATIONS)(UI: 94268556);

LEGEND:
Photomicrographs of age-matched wild-type (A,C and e) and transgenic mammary glands (b, d and f). The different transgenic strains illustrated include TG.MP1 (b), TG.MP3 (d) and TG.MP2 (f). Young nulliparous MP-1 females first demonstrated significant hyperplasia at 2 months of age (b) compared with age-matched nulliparous non-transgenic animals (a). Older, 4-month-old transgenic females from additional lines of mice had even more dramatic proliferative changes (d, TG.MP3) compared with age-matched wild-type mice (c). Finally, the mammary glands of multiparous MP2 animals, 6 months post-weaning, had extensive alveolar development with papillary epithelium lined by cells with hyperchromatic, slightly pleomorphic nuclei (f) which was not observed in age- and pregnancy-matched wild-type mice (e). Even in mice with a relatively mild phenotype (MP3), the mammary epithelium contained mitotic figures and actively secreting cells (d). Comparisons of all sets illustrate extensive lobuloalveolar development in the transgenic mice which is not seen in the wild-type mice. In particular, note the atypical hyperplasia in the main duct of the transgenic mammary gland after weaning (f). Scale bar (f), 100 :m. Standard 10-:m paraffin sections were stained with hematoxylin and eosin.

LEGEND:
Photomicrographic montage illustrating hematoxylin and eosin stained tumours found in transgenic cyclin D1 mice (x220). a, A papillary mammary adenocarcinoma from an MP1 female. b, An area from mammary tumour in the same animal illustrating squamous differentiation in a keratoacanthoma. Note the extensive laminated keratinaceous debris in the upper half of the photo (arrow). c, A uterine sarcoma from the same transgenic line (MP1) showing the densely crowded spindle cell component. This tumour resulted in extensive metastases to the liver (not shown). d, A poorly differentiated mammary adenocarcinoma with a papillary pattern in a different transgenic line (MP6). Note the adjacent non-neoplastic mammary glands in the lower right-hand corner (arrow). e, An extensive testicular sarcoma (MP1) surrounding epididymal tissue. Development of testicular tumours is consistent with the usual pattern of expression of MMTV-driven transgenes in male mice. Standard 10-:m paraffin sections were stained with haematoxylin and eosin.

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