Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression.

The proto-oncogene c-Myc plays a central role in cell growth and the development of human tumors. c-Myc interacts with Max and Myc-Max complexes bind to E-box and related sequences to activate transcription. Max also interacts with Mnt but Mnt-Max complexes repress transcription when bound to these sequences. MNT maps to human chromosome 17p13.3, a region frequently deleted in various human tumors, including mammary gland tumors. Consistent with the possibility that Mnt functions as a Myc antagonist, Mnt-deficient fibroblasts exhibit many of the hallmark characteristics of cells that overexpress Myc, and conditional (Cre/Lox) inactivation of Mnt in mammary gland epithelium leads to adenocarcinomas. Here, we further characterize mammary gland tissue following conditional deletion of Mnt in the mammary gland. We show that loss of Mnt severely disrupts mammary gland involution and leads to hyperplastic ducts associated with reduced numbers of apoptotic cells. These findings suggest that loss of Mnt in mammary tissue has similarities to Myc overexpression. We tested this directly by using promoter array analysis and mRNA expression analysis by oligonucleotide arrays. We found that Mnt and c-Myc bound to similar promoters in tumors from MMTV-c-Myc transgenic mice, and mRNA expression patterns were similar between mammary tumors from MMTV-Cre/Mnt(KO/CKO) and MMTV-c-Myc transgenic mice. These results reveal an important role for Mnt in pregnancy-associated mammary gland development and suggest that mammary gland tumorigenesis in the absence of Mnt is analogous to that caused by Myc deregulation.

Freeze/thaw stress in Ceanothus of southern California chaparral.

Freeze/thaw stress was examined in chaparral shrubs of the genus Ceanothus to determine the interactive effects of freezing and drought and to consider which is the more vulnerable component, the living leaves (symplast) or the non-living water transport system (apoplast). We hypothesized that where Ceanothus species co-occurred, the more inland species C. crassifolius would be more tolerant of low temperatures than the coastal species C. spinosus, both in terms of leaf survival (LT(50), or the temperature at which there is 50% loss of function or viability) and in terms of resistance to freezing-induced embolism (measurements of percent loss hydraulic conductivity due to embolism following freeze/thaw). Cooling experiments on 2 m long winter-acclimated shoots resulted in LT(50) values of about -10 degrees C for C. spinosus versus -18 degrees C for C. crassifolius. Freeze-thaw cycles resulted in no change in embolism when the plants were well hydrated (-0.7 to -2.0 MPa). However, when plants were dehydrated to -5.0 MPa, C. spinosus became 96% embolized with freeze/thaw, versus only 61% embolism for C. crassifolius. Stems of C. crassifolius became 90% and 97% embolized at -6.6 and -8.0 MPa, respectively, meaning that even in this species, stems could be more vulnerable than leaves under conditions of extreme water stress combined with freeze/thaw events. The dominance of C. crassifolius at colder sites and the restriction of C. spinosus to warmer sites are consistent with both the relative tolerance of their symplasts to low temperatures and the relative tolerance of their apoplasts to freeze events in combination with drought stress.