The Rexinoid LG100268 Prevents the Development of Preinvasive and Invasive Estrogen Receptor–Negative Tumors in MMTV-erbB2 Mice

Purpose: To test whether a novel rexinoid, LG100268, prevents the development of preinvasive and invasive estrogen receptor–negative mammary tumorigenesis in MMTV-erbB2 mice. Experimental Design: For invasive breast cancer prevention, MMTV-erbB2 mice were treated with daily gastric gavage of vehicle...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2007-10, Vol.13 (20), p.6224-6231
Main Authors: Li, Yuxin, Zhang, Yun, Hill, Jamal, Shen, Qiang, Kim, Hee-Tae, Xu, Xiaochun, Hilsenbeck, Susan G, Bissonnette, Reid P, Lamph, William W, Brown, Powel H
Format: Article
Language:English
Subjects:
Animals
Anticarcinogenic Agents - therapeutic use
Breast Cancer
Cell Line, Tumor
Cyclin D1 - biosynthesis
ER negative
Female
Humans
Immunohistochemistry
Ki-67 Antigen - biosynthesis
LG100268
Mammary Tumor Virus, Mouse - genetics
Mice
Mice, Transgenic
MMTV-erbB2
Neoplasm Invasiveness
Neoplasm Transplantation
Nicotinic Acids - pharmacology
Prevention
Receptor, ErbB-2 - genetics
Receptors, Estrogen - metabolism
Rexinoid
Tetrahydronaphthalenes - pharmacology
Time Factors
Transgenes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose: To test whether a novel rexinoid, LG100268, prevents the development of preinvasive and invasive estrogen receptor–negative mammary tumorigenesis in MMTV-erbB2 mice. Experimental Design: For invasive breast cancer prevention, MMTV-erbB2 mice were treated with daily gastric gavage of vehicle, LG100268 (10 mg/kg), or LG100268 (100 mg/kg) for long term starting at 3 months of age. For preinvasive lesion study, mice were treated with daily gastric gavage of vehicle or LG100268 (100 mg/kg) for 4 months. Results: Long-term treatment with LG100268 significantly prevented invasive mammary tumor development. Median time (age) to tumor development was delayed from 217 days in vehicle group to 357 days in low-dose group. In high-dose group, only 2 of 20 mice developed tumors after 430 days of treatment. Short-term treatment of LG100268 significantly prevented the development of preinvasive mammary lesions including hyperplasia and ductal carcinoma in situ . The cancer prevention effect was associated with reduced expression of Ki67 and cyclin D1 in mammary glands by >80%. Conclusion: Rexinoid LG100268 is an effective chemopreventive agent in preventing the development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-06-2681