title: Effects of short-term estrogen treatment on the progression of N-methyl-N-nitrosourea-induced premalignant mammary lesions in female Lewis rats.
abstract: We studied the effects of short-term estrogen treatment (STET) on the progression of mammary lesions from ductal hyperplasia (DH) through ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) in the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis model. Three-week-old female Lewis rats (n = 40) received an intraperitoneal injection of MNU (50 mg/kg). Three weeks later, a 3-week-release, 0.25-mg, 17β-estradiol pellet was subcutaneously implanted for 2 weeks in 20 rats (STET); the remaining 20 rats did not receive the estradiol pellets (age-matched control). All rats were killed at 12 weeks of age, and their abdominal-inguinal mammary glands were histologically examined. The incidence and multiplicity of DHs were similar between groups (STET, 90% and 3.9 ± 0.6 vs. age-matched controls, 80% and 3.0 ± 0.5). However, DCIS and IDC did not develop in STET rats, whereas DCIS (25% and 1.4 ± 0.2) and IDC (35% and 1.4 ± 0.3) developed in the age-matched controls. Immunoscores of estrogen and progesterone receptors and positive rate of proliferative cell nuclear antigen (PCNA) in DH were similar in both groups, while the positive rate of cyclin D1 was significantly reduced in the STET group (P < 0.05). Thus, STET blocked the progression from DH to DCIS in MNU-induced mammary carcinogenesis, and decreased expression of cyclin D1 may play an important role in the blockade of cell transition from DH to DCIS.
authors.affiliation: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. yurit@takii.kmu.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Lai
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kanematsu
authors.forename: Maki
authors.initials: M
authors.lastname: Kuwata
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D008770:Methylnitrosourea; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000970:Antineoplastic Agents; C530106:Ccnd1 protein, rat; D004967:Estrogens; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D008770:Methylnitrosourea