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Here we examined how the mechanism of cancer development relates to the age at exposure to ionizing radiation (IR) or the carcinogen 1\u2010methyl\u20101\u2010nitrosourea (MNU). Pre\u2010 and postpubertal (3\u2010 and 7\u2010wk\u2010old, respectively) female Sprague\u2013Dawley rats were whole\u2010body \u03b3\u2010irradiated (2\u2009Gy), injected intraperitoneally with MNU (20\u2009mg\/kg) or left untreated and were autopsied at 50\u2009wk of age. Mammary carcinomas were examined for estrogen receptor (ER) \u03b1, progesterone receptor (PR) and ErbB ligand expression and for expression microarrays. Early histological changes of the ovaries were also evaluated. The incidence of mammary cancer was higher after postpubertal, rather than prepubertal, IR exposure; the inverse was true for MNU. Most cancers were positive for both ER\u03b1 and PR except for the prepubertal IR group. Cancers of the prepubertal IR group expressed a different set of ErbB ligands from those of the other groups and did not overexpress <jats:italic>Areg<\/jats:italic>, which encodes an estrogen\u2010regulated ErbB ligand, or other developmentally related genes including those for hormonally regulated mammary gland development. Prepubertal IR exposure resulted in ovarian dysfunction as revealed by a reduced follicular pool. Evidence thus suggests that mammary carcinogenesis induced by prepubertal IR exposure is independent of ovarian hormones but requires certain ErbB ligands; induction by postpubertal exposure depends on ovarian hormones and different ErbB ligands. In contrast, the mechanism of MNU\u2010induced carcinogenesis was less influenced by the age at exposure. Mol. Carcinog. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20746","type":"journal-article","created":{"date-parts":[[2011,3,5]],"date-time":"2011-03-05T18:48:25Z","timestamp":1299350905000},"page":"539-552","source":"Crossref","is-referenced-by-count":20,"title":["Pre\u2010 and postpubertal irradiation induces mammary cancers with distinct expression of hormone receptors, ErbB ligands, and developmental genes in rats"],"prefix":"10.1002","volume":"50","author":[{"given":"Tatsuhiko","family":"Imaoka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Iizuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Ohmachi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiya","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,3,3]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.1.25"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR3082"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR0763.1"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.09027"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/13.9.1535"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20104"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20131"},{"key":"e_1_2_7_9_2","first-page":"31","volume-title":"Biology of radiation carcinogenesis","author":"Shellabarger CJ","year":"1976"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1667\/RR3502.1"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.19.8977"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0277-5379(88)90173-3"},{"key":"e_1_2_7_13_2","first-page":"5615","article-title":"Breast cancer epidemiology","volume":"48","author":"Kelsey JL","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_7_14_2","doi-asserted-by":"crossref","first-page":"909s","DOI":"10.1158\/1078-0432.909s.11.2","article-title":"Estrogen, estrogen plus progestin therapy, and risk of breast cancer","volume":"11","author":"Colditz GA","year":"2005","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-06-0045"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-4295-7_3"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013051107535"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2007.05.026"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19900501)63:9<1685::AID-CNCR2820630907>3.0.CO;2-X"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910600217"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgi100"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/16.12.3087"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.07126"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10911-008-9085-5"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20904"},{"key":"e_1_2_7_26_2","first-page":"22","volume-title":"Part I: The rat. 5. 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