Biphasic effect of short-term pregnancy hormone treatment on N-methyl-N-nitrosourea-induced mammary carcinogenesis in young and old rats

Yen Chang Lai, Takashi Yuri, Norihisa Uehara, Yoichiro Matsuoka, Sayaka Kanematsu, Airo Tsubura

Research output: Contribution to journalArticle

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Abstract

This study examined the development of N-methyl-N-nitrosourea (MNU)-induced mammary carcinomas in young and old female Lewis rats following short-term treatment with estrogen and progesterone to mimic pregnancy. Rats exposed at 4 weeks of age to MNU were treated at 6 weeks of age (early MNU/young E/P treatment) or at 24 weeks of age (early MNU/old E/P treatment) with a 21-day slow-release pellet containing 0.5 mg 17β-estradiol and 32.5 mg progesterone (E/P). Other rats were exposed to MNU at 22 and again at 23 weeks of age, and were treated with E/P at 24 weeks of age (late MNU/old E/P treatment). All experimental groups were compared with respective MNU-exposed age-matched E/P-untreated rats. Overt mammary carcinomas (≥1 cm in diameter) that were positive for hormone receptors were reduced in young E/P-treated rats, while hormone receptor-negative overt mammary carcinomas increased in old E/P-treated rats. The rate of development of small-sized mammary carcinoma (<1 cm in diameter) was similar in early MNU/young E/P-treated and late MNU/old E/P-treated groups, but higher in early MNU/old E/P-treated rats compared with respective E/P-untreated rats. At the termination of the experiment, normal mammary gland architecture had not been influenced by E/P treatment, although E/P treatment of older rats caused an increase in proliferating cell nuclear antigen (PCNA) labeling of the mammary tissue. Thus, the impact of short-term E/P treatment on MNU-induced rat mammary carcinogenesis is age-dependent and shows biphasic effects; the development of hormone-dependent overt mammary carcinomas was reduced in young rats but the development of hormone-independent overt mammary carcinomas increased in older rats. The enhanced outgrowth of hormone-independent overt mammary carcinomas by E/P treatment in old age is due to accelerated cell proliferation at the promotion/progression phase of mammary carcinogenesis. Age at short-term E/P treatment is crucial for breast cancer control.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalMolecular medicine reports
Volume2
Issue number2
DOIs
Publication statusPublished - Aug 31 2009
Externally publishedYes

Fingerprint

Methylnitrosourea
Rats
Carcinogenesis
Breast
Hormones
Pregnancy
Breast Neoplasms
Progesterone
Proliferating Cell Nuclear Antigen
Cell proliferation
Human Mammary Glands
Labeling
Estradiol
Estrogens

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

Cite this

Biphasic effect of short-term pregnancy hormone treatment on N-methyl-N-nitrosourea-induced mammary carcinogenesis in young and old rats. / Lai, Yen Chang; Yuri, Takashi; Uehara, Norihisa; Matsuoka, Yoichiro; Kanematsu, Sayaka; Tsubura, Airo.

In: Molecular medicine reports, Vol. 2, No. 2, 31.08.2009, p. 213-220.

Research output: Contribution to journalArticle

Lai, Yen Chang ; Yuri, Takashi ; Uehara, Norihisa ; Matsuoka, Yoichiro ; Kanematsu, Sayaka ; Tsubura, Airo. / Biphasic effect of short-term pregnancy hormone treatment on N-methyl-N-nitrosourea-induced mammary carcinogenesis in young and old rats. In: Molecular medicine reports. 2009 ; Vol. 2, No. 2. pp. 213-220.
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