Mitotic activity, apoptosis and TRPM-2 mRNA expression in DMBA-induced rat mammary carcinoma treated with anti-estrogen toremifene.

Abstract:

:Anti-estrogen toremifene inhibits growth of the 7,12-dimethylbenz(a)anthracene(DMBA)-induced rat mammary carcinoma. The changes in proliferation and cell death were studied in detail. Proliferation was measured by counting mitotic figures in histologic sections, expressed by volume-corrected mitotic index (M/V INDEX). Respective volume corrected apoptotic index (A/V INDEX) was measured by counting apoptotic nuclei in the same sections. The presence of apoptotic cells was confirmed by transmission electron microscopy. In the untreated tumors, both mitosis and apoptosis were frequent. In the toremifene-treated tumors, the mean M/V INDEX was about half of the mean M/V INDEX in the untreated control tumors. The mean A/V INDEX in the toremifene-treated tumors was about 3/4 of the mean A/V INDEX in the controls. In toremifene-treated tumors, A/V INDEX was strongly correlated with TRPM-2-gene expression, which was also enhanced when compared with the controls. TRPM-2 gene has been associated with programmed cell death induced by hormonal ablation in prostate- and breast-cancer cells. No such correlation was seen in control tumors. These findings suggest that, in the DMBA-tumor model, toremifene affects the cell turnover by inhibiting mitotic activity and modifying abundant spontaneous apoptosis. In this model, the inhibition of tumor growth results mostly from reduction of mitotic activity.

journal_name

Int J Cancer

authors

Huovinen R,Wärri A,Collan Y

doi

10.1002/ijc.2910550429

subject

Has Abstract

pub_date

1993-10-21 00:00:00

pages

685-91

issue

4

eissn

0020-7136

issn

1097-0215

journal_volume

55

pub_type

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