title: Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells.
abstract: Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Therefore, we have first examined the intratumoral localization of aromatase mRNA/protein in 19 breast carcinomas using laser capture microdissection/quantitative reverse transcription-PCR (RT-PCR) and immunohistochemistry. Aromatase mRNA and protein were detected in both intratumoral stromal and parenchymal cells in breast carcinoma tissues. Subsequent microarray expression profiling and clustering analyses, in addition to quantitative RT-PCR studies, showed a significant positive correlation between aromatase and estrogen-related receptor alpha mRNA expression in isolated carcinoma cells. We further examined an interaction between stromal cells isolated from human breast carcinoma tissues and breast carcinoma cell lines using a coculture system to study the biological characteristic of aromatase expression in carcinoma cells. Aromatase mRNA and enzyme activity and 17beta-hydroxysteroid dehydrogenase type 1 mRNA in breast carcinoma cell lines, including MCF-7 and SK-BR-3 cells, were up-regulated in the presence of patient-derived 32N or 74T intratumoral stromal cells. The results from steroid conversion assays were also consistent with the findings above. The results of our study also showed that aromatase inhibitors were more effective in inhibiting aromatization induced by coculture in MCF-7 than that in stromal 32N. The examination of the localization of aromatase and its regulation, including the interactions existing between different cell types in human breast carcinoma tissues, may provide important information as to achieving better clinical response to aromatase inhibitors in breast cancer patients.
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Yasuhiro
authors: Y
authors: Miki
authors: Takashi
authors: T
authors: Suzuki
authors: Chika
authors: C
authors: Tazawa
authors: Yuri
authors: Y
authors: Yamaguchi
authors: Kunio
authors: K
authors: Kitada
authors: Seijiro
authors: S
authors: Honma
authors: Takuya
authors: T
authors: Moriya
authors: Hisashi
authors: H
authors: Hirakawa
authors: Dean B
authors: DB
authors: Evans
authors: Shin-Ichi
authors: S
authors: Hayashi
authors: Noriaki
authors: N
authors: Ohuchi
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D004967:Estrogens; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase