Inhibition of estrogen-induced mammary tumor formation in MMTV-aromatase transgenic mice by 4-chlorophenylacetate

Neil Sidell, Nameer B Kirma, Eddie T. Morgan, Hareesh Nair, Rajeshwar R Tekmal

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)302-310
Number of pages9
JournalCancer Letters
Volume251
Issue number2
DOIs
StatePublished - Jun 28 2007

Fingerprint

Aromatase
Transgenic Mice
Estrogens
Breast Neoplasms
Estrogen Receptors
Aromatase Inhibitors
Neoplasms
9,10-Dimethyl-1,2-benzanthracene
Tamoxifen
Therapeutics
Human Mammary Glands
Endometrium
Osteoporosis
4-chlorophenylacetic acid
Breast
Fatty Acids
Bone and Bones
Growth

Keywords

  • 4-Chlorophenylacetate
  • Antiestrogen
  • Breast cancer
  • Estrogen receptor

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Inhibition of estrogen-induced mammary tumor formation in MMTV-aromatase transgenic mice by 4-chlorophenylacetate. / Sidell, Neil; Kirma, Nameer B; Morgan, Eddie T.; Nair, Hareesh; Tekmal, Rajeshwar R.

In: Cancer Letters, Vol. 251, No. 2, 28.06.2007, p. 302-310.

Research output: Contribution to journalArticle

Sidell, Neil ; Kirma, Nameer B ; Morgan, Eddie T. ; Nair, Hareesh ; Tekmal, Rajeshwar R. / Inhibition of estrogen-induced mammary tumor formation in MMTV-aromatase transgenic mice by 4-chlorophenylacetate. In: Cancer Letters. 2007 ; Vol. 251, No. 2. pp. 302-310.
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