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Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells.
Cancer Res. 2007 Apr 15; 67(8):3945-54.CR

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+Show Affiliations

Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17440110

Citation

Miki, Yasuhiro, et al. "Aromatase Localization in Human Breast Cancer Tissues: Possible Interactions Between Intratumoral Stromal and Parenchymal Cells." Cancer Research, vol. 67, no. 8, 2007, pp. 3945-54.
Miki Y, Suzuki T, Tazawa C, et al. Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells. Cancer Res. 2007;67(8):3945-54.
Miki, Y., Suzuki, T., Tazawa, C., Yamaguchi, Y., Kitada, K., Honma, S., Moriya, T., Hirakawa, H., Evans, D. B., Hayashi, S., Ohuchi, N., & Sasano, H. (2007). Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells. Cancer Research, 67(8), 3945-54.
Miki Y, et al. Aromatase Localization in Human Breast Cancer Tissues: Possible Interactions Between Intratumoral Stromal and Parenchymal Cells. Cancer Res. 2007 Apr 15;67(8):3945-54. PubMed PMID: 17440110.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells. AU - Miki,Yasuhiro, AU - Suzuki,Takashi, AU - Tazawa,Chika, AU - Yamaguchi,Yuri, AU - Kitada,Kunio, AU - Honma,Seijiro, AU - Moriya,Takuya, AU - Hirakawa,Hisashi, AU - Evans,Dean B, AU - Hayashi,Shin-Ichi, AU - Ohuchi,Noriaki, AU - Sasano,Hironobu, PY - 2007/4/19/pubmed PY - 2007/5/24/medline PY - 2007/4/19/entrez SP - 3945 EP - 54 JF - Cancer research JO - Cancer Res VL - 67 IS - 8 N2 - 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/17440110/Aromatase_localization_in_human_breast_cancer_tissues:_possible_interactions_between_intratumoral_stromal_and_parenchymal_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17440110 DB - PRIME DP - Unbound Medicine ER -