Antibody blockage of MIF significantly reduced (by 75%) intimal macrophage infiltration in ApoE−/− mice undergoing spontaneous atherosclerosis and diminished the aortic plaque area.
In an elegant study, Sternlicht et al. [ 42] showed that transgenic mice that express an auto-activating form of MMP-3/stromelysin-1, under the control of the whey acidic protein gene promoter, undergo spontaneous development of premalignant and malignant lesions in the mammary glands when compared to their non-transgenic littermates.
Furthermore, ROS, NO generation and inducible nitric oxide synthase (iNOS) expression were enhanced in a time-dependent manner in human PMNs and mice BMDN undergoing spontaneous apoptosis.
The syngeneic mouse ovarian surface epithelial (MOSE) cells, derived from the C57BL6 mice, have undergone spontaneous transformation in cell culture.
Inactivation of the bax gene noticeably delayed ovarian senescence in female mice [2], [3], and significantly reduced the number of oocytes undergoing spontaneous and chemotherapy-induced apoptosis.
As for male germ cells, Di Agostino and co-workers [17] have shown that isolated mouse pachytene spermatocytes cultured under SM undergo spontaneous meiotic progression.
In fact, chronic hepatic SAM deficiency in a certain mouse strain (i.e., Mat1a knockout mice) resulted in spontaneous development of HCC (Martinez-Chantar et al. 2002).
Furthermore, they did not acquire anchorage-independent growth capacity and did not develop into tumors in immunodeficient mice, suggesting that hepatic oval cells do not undergo spontaneous malignant transformation.
Smurf2-null mouse embryonic fibroblasts (MEFs) exhibit impaired senescence responses, and undergo spontaneous transformation more frequently in culture.
We found that Mdr2 −/− MEFs undergo spontaneous transformation and that Mdr2 −/− mice are more susceptible to chemical carcinogen-induced intestinal tumorigenesis.
In contrast, PTP1B effectively inhibits signaling of several oncogenic tyrosine kinases [ 50], while inactivation of the gene in TP53 knockout mice accelerates the spontaneous development of lymphomas [ 32].
