Inhibition of estrogen-induced mammary tumor formation in MMTV-aromatase transgenic mice by 4-chlorophenylacetate.
Treatment of estrogen-sensitive breast cancer with selective estrogen selective modulators (SERMs) and, more recently, aromatase inhibitors has met with wide success. However, antagonism of estrogen receptor (ER) activity in breast carcinomas by SERMs such as tamoxifen has been associated with increased risk of cancer in other tissue such as the endometrium. Furthermore, current therapies using aromatase inhibitors have side effects on bone resulting in development of osteoporosis in some patients. We present in this paper the results of a study using 4-chlorophenylacetate (4-CPA), a compound which belongs to a family of small aromatic fatty acids that has been shown to possess anticancer properties, to treat DMBA exposed MMTV-aromatase mice. These animals exhibit elevated levels of estrogen in their mammary glands and develop estrogen-responsive tumors. Consistent with our earlier findings showing that 4-CPA inhibited the growth of ER positive breast cancer cells in vitro, we now demonstrate that this compound inhibits tumor formation in MMTV-aromatase mice. This effect was not associated with reduction of ER expression in their mammary tissue, or to alteration of aromatase levels or activity. The data suggest that 4-CPA is a novel therapeutic agent that could be used in the prevention or treatment of estrogen-sensitive breast cancer.
Sidell
Neil
N
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA, USA. nsidell@emory.edu
Kirma
Nameer
N
Morgan
Eddie T
ET
Nair
Hareesh
H
Tekmal
Rajeshwar Rao
RR
D000818:Animals; D001141:Aromatase / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009376:Neoplasms, Hormone-Dependent / Q000517:prevention & control; D010648:Phenylacetates / Q000494:pharmacology*; D011991:Receptors, Virus / Q000235:genetics*
D004967:Estrogens; C111417:Fam89b protein, mouse; D008565:Membrane Proteins; D010648:Phenylacetates; D011991:Receptors, Virus; C029716:4-chlorophenylacetic acid; D001141:Aromatase