In vivo AP-1 blockade by Tam67 suppresses erbB2-induced mammary tumorigenesis. A, treatment scheme. The adult trigenic pUHD-Tam67/MMTV-rtTA/MMTV-erbB2 mice together with other unitransgenic and bitransgenic control mice were fed either regular water or doxycycline (Dox)-water at the age of 3 mo (13 wk) for the entire duration of experiment. Mice that developed mammary tumors ≥1,000 mm3 were sacrificed for pathologic examination. B, Kaplan-Meier plot of the proportion of animals free of mammary tumors versus weeks of age is shown for the trigenic pUHD-Tam67/MMTV-rtTA/MMTV-erbB2 mice. Control group (n = 16) were fed regular drinking water, whereas AP-1-blocked group (n = 18) were fed doxycycline-water to turn on Tam67 expression in the mammary glands. Tumor measurements were made twice per week. Statistical analysis was done with the generalized Wilcoxon test. C, bigenic mice with erbB2 and rtTA transgenes but without the Tam67 gene were divided into two groups. All animals have normal AP-1 activity. Doxycycline(-) group [D(-); n = 22] were fed regular drinking water, whereas doxycycline(+) group [D(+); n = 25] were fed doxycycline-water as control for doxycycline effect. Kaplan-Meier plot and statistical analysis are treated the same as described in B. D, bigenic mice with erbB2 and Tam67 transgenes but without the activator rtTA gene were divided into two groups. All animals have normal AP-1 activity. Doxycycline(-) group (n = 32) were fed regular drinking water, whereas doxycycline(+) group (n = 31) were fed doxycycline-water as control for doxycycline effect. Kaplan-Meier plot and statistical analysis are treated the same as described in B. E, unigenic mice with erbB2 transgene but without the activator rtTA gene and Tam67 transgene were divided into two groups. All animals have normal AP-1 activity. Doxycycline(-) group (n = 15) were fed regular drinking water, whereas doxycycline(+) group (n = 19) were fed doxycycline-water as control for doxycycline effect. Kaplan-Meier plot and statistical analysis are treated the same as described in B.