The Rexinoid LG100268 prevents the development of preinvasive and invasive estrogen receptor negative tumors in MMTV-erbB2 mice.
OBJECTIVE
To test whether a novel rexinoid, LG100268, prevents the development of preinvasive and invasive estrogen receptor-negative mammary tumorigenesis in MMTV-erbB2 mice.


METHODS
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%.


CONCLUSIONS
Rexinoid LG100268 is an effective chemopreventive agent in preventing the development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.
Li
Yuxin
Y
Breast Center, Department of Medicine, Baylor College of Medicine, Houston TX 77030, USA.
Zhang
Yun
Y
Hill
Jamal
J
Shen
Qiang
Q
Kim
Hee-Tae
HT
Xu
Xiaochun
X
Hilsenbeck
Susan G
SG
Bissonnette
Reid P
RP
Lamph
William W
WW
Brown
Powel H
PH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009539:Nicotinic Acids / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013997:Time Factors; D019076:Transgenes
D016588:Anticarcinogenic Agents; D019938:Cyclin D1; D019394:Ki-67 Antigen; D009539:Nicotinic Acids; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013764:Tetrahydronaphthalenes; C095104:LG 100268