ER-activating ability of breast cancer stromal fibroblasts is regulated independently of alteration of TP53 and PTEN tumor suppressor genes

• Published in: Biochemical and biophysical research communications 2012-11, Vol.428 (2), p.259-263
• Main Authors: Suda, Tetsuji, Oba, Hanako, Takei, Hiroyuki, Kurosumi, Masafumi, Hayashi, Shin-ichi, Yamaguchi, Yuri
• Format: Article
• Language: English
• Subjects: Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Carcinoma - genetics; Carcinoma - pathology; Carcinoma-associated fibroblasts (CAF); Cell Line, Tumor; Estrogen; Estrogen receptor (ER); Female; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Dosage; Gene Expression Regulation, Neoplastic; Humans; PTEN Phosphohydrolase - genetics; Receptors, Estrogen - metabolism; Stromal Cells - metabolism; Stromal Cells - pathology; Tumor Suppressor Protein p53 - genetics
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.10.035

► Carcinoma-associated fibroblasts (CAFs) are able to activate estrogen receptor (ER) in breast cancer. ► CAF-specific ER-activating ability varied among individual cases. ► Breast CAFs maintained wild-type alleles for TP53 and PTEN. ► Copy number aberrations in these tumor suppressor genes were not observed in any CAFs. ► ER-activating ability of the CAFs is regulated independently of aberrations in these genes. Carcinoma-associated fibroblasts (CAFs) are associated with tumor progression and metastasis, and are able to activate estrogen receptor (ER) in breast cancer. We established a stable transformant of a human breast cancer cell line to detect CAF-specific ER-activating ability, and found that this CAF ability varied among tumors. Some studies have reported a high frequency of alterations among tumor suppressor genes in stromal cells, but do not generally agree as to the frequency. Moreover, the activation mechanism of CAF-induced estrogen signals, including the effects of these gene aberrations, is not fully understood. We investigated the relevance of tumor suppressor gene aberrations and ER-activating ability in CAFs derived from 20 breast cancer patients. Although CAF-specific ER-activating abilities varied among individual cases, all CAFs maintained wild-type alleles for TP53 and PTEN. Also, copy number aberrations in these genes were not observed in any CAFs. Our results suggest that the ER-activating ability of the CAFs is regulated independently of aberrations in these genes; and that other mechanisms of tumor–stromal interaction may affect activation of estrogen signals in breast cancer.