Table 1.

Histopathology and metastatic potential of MMTV-PyMT and MMTV-ErbB2/Neu mammary adenocarcinomas developing in wt, Akt1−/−, Akt2−/−, and Akt3−/− mice

PyMTNeu
wtAkt1−/−Akt2−/−Akt3−/−wtAkt1−/−Akt2−/−Akt3−/−
Tumor growth pattern
    Solid16/1612/167/1210/1010/103/312/1211/11
    Papillary8/167/1612/124/102/100/39/120/11
    Glandular6/166/164/124/101/100/34/122/11
    Cribriform3/163/162/102/102/101/33/122/11
    Cystic-dilated ducts1/163/1610/122/101/100/310/121/11
Fibrosis16/1616/1612/1210/102/102/35/1210/11
Grade22–3222–3222
Invasion16/1616/1612/1210/102/103/35/126/11
Metastasis
    Lung metastasis15/166/166/129/104/102/34/125/11
    Vascular3/42/32/43/5
    Parenchyma15/156/66/69/91/40/32/42/5
  • NOTE: For PyMT: All the tumors arising in PyMT/wt and PyMT/Akt3−/− mice were characterized by a predominantly solid growth pattern, interspersed with areas of papillary, glandular, and cribriform growth in some of the mice. Only some of the tumors arising in PyMT/Akt1−/− and PyMT/Akt2−/− mice on the other hand exhibited a solid growth pattern. All the tumors arising in PyMT/Akt2−/− mice exhibited papillary growth. PyMT/Akt1−/−-induced tumors tended to exhibit a more malignant histologic grade than PyMT-induced tumors arising in other genetic backgrounds. The tumors arising in both the wt and the Akt knockout mice were all invasive. However, invasiveness did not correlate with metastasis in that PyMT/Akt1−/− and PyMT/Akt2−/− tumors were significantly less metastatic (P < 0.0021 and P < 0.00228, respectively). Serial sections of the lungs of tumor-bearing mice sacrificed when their primary tumors approaches 2 cm in diameter. For Neu: Mammary tumors arising in Neu/wt mice were shown to exhibit a predominantly solid growth pattern, and their histologic grade was evenly divided between grades 2 and 3. Papillary differentiation was noted only in the tumors arising in Neu/Akt2−/− mice, which exhibited a distinct solid papillary growth pattern. The differences in the frequency of invasiveness between Neu-induced tumors in wt and Akt2−/− or Akt3−/− mice were not statistically significant. Interestingly, at the time of this report, only three Neu/Akt1−/− mice had developed tumors and all three of them were invasive, suggesting that tumors arising in mice lacking Akt1 may be more invasive than tumors arising in mice of all other genetic backgrounds (P < 0.0350). Because we had only three Akt1−/− tumors to date, we cannot exclude the possibility that ablation of Akt1 in the Neu model may also increase the rate of metastasis.