Fig 1: Lactation inhibits the oncogenic effect of PAPP-A AIncidence of spontaneous mammary tumor formation in PAPP-A females relative to the duration of lactation. Long lactation of > 3 weeks ranges from 21 to 24 days, with an average of 21.25 days, while short lactation of < 2 weeks ranges from 0 to 13 days, with an average of 1.076 days. Fisher's exact test: P = 0.0170.B–DGrowth rate of ctl and p-a xenografts injected in fat pad of actively involuting mammary glands without any prior lactation (-Inv.), of actively lactating (-Lac.), and of actively involuting mammary glands following 2 weeks of prior lactation (-Lac.+Inv.), (n = 3 mice, 6 tumors total, mean ± SD). Unpaired t-test (two-tailed) was applied to calculate statistical significance at the end point. **P = 0.0027 for (B), P = 0.4359 for (C), and P = 0.3066 for (D).EWhole-mount analyses of involuting mammary glands (n = 12 mice; three mice per time point) at days 1, 3, 6, and 12 of involution in NT and PAPP-A females, scale bar: 1 mm.FH&E sections of corresponding mammary glands from (E), scale bar: 100 µm.GImmunoblot of mammary glands during involution in NT and PAPP-A females.HImmunoblot for STC1 and STC2 from mammary gland extracts of virgin (V), at pregnancy (P), at lactation (L), or at involution (I) performed in triplicate mice per group.IQuantification of immunoblot for STC1 or STC2 from (H). Error bars are mean ± SD. Left panel (STC1) *P = 0.0148 (V versus I), *P = 0.0293 (P versus I), **P = 0.0021 (L versus I). Right panel (STC2) *P = 0.0248 (V versus L), **P = 0.0079 (L versus I).JImmunoblot of rIGFBP-5 following proteolysis assay using NT or PAPP-A extracts from V, P, L or I mammary glands. Source data are available online for this figure.