No abstract

Background:The vasoconstricting thromboxane A 2 prostanoid receptor (TP) is physically coupled to the MaxiK channel ␣-subunit, down-regulating its activity, but the role of the MaxiK ␤1-subunit is unknown. Results: The MaxiK ␤1-subunit can interact with TP independently of the MaxiK ␣-subunit and counteracts activated TPinduced current inhibition, and its ablation increases TP vasoconstricting potency. Conclusion: The ␤1-subunit modifies TP actions. Significance: This is the first demonstration that the MaxiK ␤1-subunit associates with a vasoconstricting receptor.

PTEN tumor suppressor is frequently mutated in human cancers, including breast cancers. Female patients with inherited PTEN mutations suffer from virginal hypertrophy of the breast with high risk of malignant transformation. However, the exact mechanisms of PTEN in controlling mammary gland development and tumorigenesis are unclear. In this study, we generated mice with a mammary-specific deletion of the Pten gene. Mutant mammary tissue displayed precocious lobulo-alveolar development, excessive ductal branching, delayed involution and severely reduced apoptosis. Pten null mammary epithelial cells were disregulated and hyperproliferative. Mutant females developed mammary tumors early in life. Similar phenotypes were observed in Pten-null mammary epithelia that had been transplanted into wild-type stroma, suggesting that PTEN plays an essential and cell-autonomous role in controlling the proliferation, differentiation and apoptosis of mammary epithelial cells.

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Mouse mammary tumor virus (MMTV) has frequently been used as an insertional mutagen to identify provirally activated mammary proto-oncogenes. To expedite and facilitate the process of cloning MMTV insertion sites, we have introduced a bacterial supFsuppressor tRNA gene into the long terminal repeat (LTR) of MMTV, thus allowing selection of clones containing it in lambda vectors bearing amber mutations. The presence of supF in the LTR should circumvent the screening process for proviral insertion sites, since only those lambda clones with supF-containing proviral-cellular junction fragments should be able to form plaques on a lawn of wild-type Escherichia coli (i.e., lackingsupF). The resulting virus (MMTVsupF) induced mammary tumors at the expected rate in infected mice, deleted the appropriate T-cell population by virtue of its superantigen gene, and stably retained the supF gene after passage via the milk to female offspring. To test the selective function of the system, size-selected DNA containing two proviral-cellular junction fragments from an MMTV supF-induced mammary tumor was ligated into λgtWES.λB, packaged, and plated on a supF-deficient bacterial host for selection of supF-containing clones. All plaques tested contained the desired cloned fragments, thus demonstrating the utility of this modified provirus for the rapid cloning of MMTV insertion sites.