Reference SummaryShibata MA, Carcinogenesis 2003 Mar;24(3):453-9

Title

Comparative effects of lovastatin on mammary and prostate oncogenesis in transgenic mouse models.

Authors

Shibata MA; Kavanaugh C; Shibata E; Abe H; Nguyen P; Otsuki Y; Trepel JB; Green JE

Journal

Carcinogenesis

Volume

24

Issue

3

Year

2003

Pages

453-9

Abstract

The effects of lovastatin, a potent inhibitor of HMG CoA reductase, on experimental mammary and prostate oncogenesis, were studied in vitro and in vivo. Lovastatin inhibited cell growth in vitro in a dose-dependent manner for both mammary and prostate cancer cell lines, which was associated with p53-independent apoptosis. Flow cytometric analyses of lovastatin-treated mammary and prostate cancer cells demonstrated cell-cycle G(1) arrest, as well as decreases in S and G(2)/M fractions. p21(Waf1) and p27(Kip1) were induced by lovastatin in both types of cancer cells. Gene expression profiling of cells treated with lovastatin, however, was remarkable for a paucity of transcriptional changes induced by lovastatin. Treatment with lovastatin for 4 weeks did inhibit the formation of pre-neoplastic mammary intraepithelial neoplasias (MIN) in vivo, but not invasive carcinomas in the C3(1)/SV40 TAg transgenic model of mammary cancer. The decreased multiplicity of MIN lesions was associated with increased levels of apoptosis in these lesions. However, cell proliferation in the mammary lesions was not significantly different between lovastatin-treated and control mice 1 day after lovastatin treatment. In female mice treated with lovastatin for 12 weeks, there was a tendency for reduced tumor volume, which did not reach statistical significance. However, lovastatin did not suppress any lesion formation in the prostate of C3(1)/SV40 TAg transgenic male mice. Our results suggest that as lovastatin exerts an inhibitory effect on the development of early mammary lesions of mammary carcinogenesis, this compound may be useful for the chemoprevention of mammary cancer and might have utility as an adjuvant in breast cancer therapy. The chemopreventive effects of lovastatin in vivo, however, may be tissue-specific.

Links

J:82837 – Mouse Genome Informatics
12663504 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/N-Tg(C3-1-TAg)cJeg Mammary gland adenocarcinoma
  • lovastatin
Mammary gland

observed

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland adenocarcinoma Mammary gland

very high

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland mammary intraepithelial neoplasia (MIN) - high grade
  • lovastatin
Mammary gland

observed

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland mammary intraepithelial neoplasia (MIN) - high grade Mammary gland

very high

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland mammary intraepithelial neoplasia (MIN) - low grade Mammary gland

100

FVB/N-Tg(C3-1-TAg)cJeg Mammary gland mammary intraepithelial neoplasia (MIN) - low grade
  • lovastatin
Mammary gland

observed

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe carcinoma Prostate gland - Dorsolateral lobe

10

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe carcinoma
  • lovastatin
Prostate gland - Dorsolateral lobe

0

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe prostatic intraepithelial neoplasia - high grade (HGPIN)
  • lovastatin
Prostate gland - Dorsolateral lobe

64

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland - Dorsolateral lobe

50

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe prostatic intraepithelial neoplasia - low grade (LGPIN)
  • lovastatin
Prostate gland - Dorsolateral lobe

100

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Dorsolateral lobe prostatic intraepithelial neoplasia - low grade (LGPIN) Prostate gland - Dorsolateral lobe

100

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe carcinoma Prostate gland - Ventral lobe

30

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe carcinoma
  • lovastatin
Prostate gland - Ventral lobe

24

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe prostatic intraepithelial neoplasia - high grade (HGPIN)
  • lovastatin
Prostate gland - Ventral lobe

76

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe prostatic intraepithelial neoplasia - high grade (HGPIN) Prostate gland - Ventral lobe

60

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe prostatic intraepithelial neoplasia - low grade (LGPIN)
  • lovastatin
Prostate gland - Ventral lobe

100

FVB/N-Tg(C3-1-TAg)cJeg Prostate gland - Ventral lobe prostatic intraepithelial neoplasia - low grade (LGPIN) Prostate gland - Ventral lobe

100