E4F1, a novel estrogen-responsive gene in possible atheroprotection, revealed by microarray analysis

Yasuhiro Nakamura, Katsuhide Igarashi, Takashi Suzuki, Jun Kanno, Tohru Inoue, Chika Tazawa, Masayuki Saruta, Tomoko Ando, Noriko Moriyama, Toru Furukawa, Masao Ono, Takuya Moriya, Kiyoshi Ito, Haruo Saito, Tadashi Ishibashi, Shoki Takahashi, Shogo Yamada, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Estrogen has been postulated to be involved in inhibition of vascular smooth muscle cell (VSMC) proliferation mainly via estrogen receptor (ER), but the detailed mechanism has remained primarily unknown. Therefore, in this study, microarray analysis was used in two types of cultured human VSMCs: one positive for ERα, and the other for ERβ, which were treated by estrogens to detect the estrogen-responsive genes. We also used quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate mRNA levels of selective target gene (TG) in these cells. We further studied whether the TG product was involved in inhibition of proliferation using small interfering RNA (siRNA) of the TG transfection. We subsequently used quantitative RT-PCR and in situ hybridization analysis to evaluate the expression of these gene products in human aorta. E4F1, a possible inducer of cell growth arrest, was markedly increased only in ERα-positive VSMCs by estrogens in both microarray and RT-PCR analyses. Blocking of E4F1 using siRNA suppressed estrogenic inhibition of ERα-positive VSMC proliferation. E4F1 mRNA was abundant in premenopausal female aorta with mild atherosclerotic changes. E4F1 is therefore considered one of the estrogen-responsive genes involving ERα-mediated inhibition of VSMC proliferation and may play an important role in estrogen-related atheroprotection of human aorta.

Original languageEnglish
Pages (from-to)2019-2031
Number of pages13
JournalAmerican Journal of Pathology
Issue number6
Publication statusPublished - 2004 Dec


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