Fertile Ground for Cancer Proteins

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Science  21 Dec 2007:
Vol. 318, Issue 5858, pp. 1835
DOI: 10.1126/science.318.5858.1835b

Leukemia inhibitory factor (LIF) is a secreted glycoprotein first identified, as its name implies, as a regulator of leukemic cell differentiation. More recently, attention has focused on the role of this cytokine in the female reproductive tract. In mice, LIF is one of the few molecules known to be required for implantation of the blastocyst, or earlystage embryo, into the uterus. Thus, it has been hypothesized that drugs targeting LIF activity could (depending on their mode of action) be used either to enhance fertility by promoting implantation or as contraceptives that prevent implantation. Progress on the latter front is reported by White et al., who have developed a potent LIF antagonist that is completely effective in blocking blastocyst implantation when administered systemically to mice. Whether this antagonist—a chemically stabilized mutant version of LIF that binds to its receptor but does not trigger downstream signals—has similar activity in primates remains to be explored. In independent work, Hu et al. find that LIF expression in the mouse uterus is positively regulated at the transcriptional level by p53, an intensely studied tumor suppressor protein. Discovery of this link between LIF and p53 raises the possibility that cancer drugs designed to activate p53 might be useful tools for investigating the mechanisms underlying blastocyst implantation or as an alternative means of enhancing fertility. — PAK

Proc. Natl. Acad. Sci. U.S.A. 104, 19357 (2007); Nature 450, 721 (2007).

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