ER-activating ability of breast cancer stromal fibroblasts is regulated independently of alteration of TP53 and PTEN tumor suppressor 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.
Research Institute for Clinical Oncology, Saitama Cancer Center, Ina-machi, Saitama 362-0806, Japan.
Tetsuji
T
Suda
Hanako
H
Oba
Hiroyuki
H
Takei
Masafumi
M
Kurosumi
Shin-ichi
S
Hayashi
Yuri
Y
Yamaguchi
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D011960:Receptors, Estrogen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human