Journal Article

Neoplastic transformation of mammary epithelial cells in rats is associated with decreased apoptotic cell death

Anne Shilkaitis, Albert Green, Vernon Steele, Ronald Lubet, Garry Kelloff and Konstantin Christov

in Carcinogenesis

Volume 21, issue 2, pages 227-233
Published in print February 2000 | ISSN: 0143-3334
Published online February 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.2.227
Neoplastic transformation of mammary epithelial cells in rats is associated with decreased apoptotic cell death

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Previous studies have shown that terminal end buds (TEBs) in the murine mammary gland have high proliferative activity and demonstrate apoptotic cell death (ACD). Since TEBs are considered the place of origin of most chemically induced mammary carcinomas, we hypothesized that the development of hyperplastic and premalignant (carcinoma in situ, CIS) lesions in TEBs is associated with either a further increase in cell proliferation and/or with a decrease in ACD. To test this hypothesis we used the N-methyl-N-nitorosourea (MNU) carcinogenesis model in rats, where the occurrence of mammary tumors is preceded by hyperplastic and premalignant lesions arising mostly in TEBs, as well as in ducts and alveoli. The percentage of proliferating cells, as evaluated by 5-bromodeoxyuridine labeling (BrdU-LI), was similar in TEBs to those in terminal endbud hyperplasia (TEBH), CIS, and carcinomas (CA), whereas the percentage of apoptotic cells (apoptotic index, AI) was relatively high in TEBs and decreased in TEBH, CIS, and CA. This indicates that neoplastic transformation of mammary epithelial cells in TEBs is not associated with an increase in cell proliferation, but with a decrease in ACD. In addition to TEBH, hyperplastic lesions developed in ductal branching areas (ductal hyperplasia, DH) and alveolar structures (alveolar hyperplasia, AH). However, BrdU-LI in both DH and AH was lower than in TEBH, whereas the AI values were similar, suggesting that TEBH has a higher potential for progression and malignant transformation than DH and AH. In mammary tumors apoptotic cells were rare in the peripheral, proliferative areas, but frequent close to the necrotic areas, suggesting that intratumoral factors may significantly affect ACD. Thus, it appears that dissociation between cell proliferation and apoptosis occurs in the hyperplastic stages of mammary carcinogenesis and that neoplastic transformation of mammary epithelial cells is associated with decreased ACD but not with increased cell proliferation.

Keywords: ACD, apoptotic cell death; AH, alveolar hyperplasia; AI, percentage of apoptotic cells; BrdU, 5-bromodeoxyuridine; BrdU-LI, percentage of cells labeled by BrdU; CA, carcinoma; CIS, carcinoma in situ; DH, ductal hyperplasia; DMBA, dimethylbenzanthracene; MECs, mammary epithelial cells; MNU, N-methyl-N-nitrosourea; TEBs, terminal end buds; TEBH, terminal end bud hyperplasia.

Journal Article.  4911 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.