title: Molecular mechanisms regulating the hormone sensitivity of breast cancer.
abstract: Breast cancer is a heterogeneous disease. Approximately 70% of breast cancers are estrogen receptor (ER) positive. Endocrine therapy has dramatically improved the prognosis of ER-positive breast cancer; however, many tumors exhibit de novo or acquired resistance to endocrine therapy. A thorough understanding of the molecular mechanisms regulating hormone sensitivity or resistance is important to improve the efficacy of and overcome the resistance to endocrine therapy. The growth factor receptor signaling pathways, particularly the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway can mediate resistance to all forms of endocrine therapy. In contrast, FOXA1 transcription factor is a key determinant of ER function and endocrine response. Intriguingly, a link between hormone resistance induced by the PI3K/Akt/mTOR pathway and the function of FOXA1 has been suggested. In this review, we focus on the PI3K/Akt/mTOR pathway and functions of FOXA1 in terms of the molecular mechanisms regulating the hormone sensitivity of breast cancer.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Comprehensive Clinical Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hisamatsu
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Nami
authors.initials: N
authors.lastname: Yamashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D051541:Hepatocyte Nuclear Factor 3-alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011960:Receptors, Estrogen; D058570:TOR Serine-Threonine Kinases; C496499:FOXA1 protein, human
keywords: Breast cancer; FOXA1; PI3K/Akt/mTOR pathway; endocrine therapy; estrogen receptor