title: [The role of protein kinase PAK1 in the regulation of estrogen-independent growth of breast cancer].
abstract: The main goal of this work was to study the intracellular signaling pathways responsible for the development of hormone resistance and maintaining the autonomous growth of breast cancer cells. In particular, the role of PAK1 (p21-activated kinase 1), the key mitogenic signaling protein, in the development of cell resistance to estrogens was analyzed. In vitro studies were performed on cultured breast cancer cell lines: estrogen-dependent estrogen receptor (ER)-positive MCF-7 cells and estrogen-resistant ER-negative HBL-100 cells. We found that the resistant HBL-100 cells were characterized by a higher level of PAK1 and demonstrated PAK1 involvement in the maintaining of estrogen-independent cell growth. We have also shown PAK1 ability to up-regulate Snail1, one of the epithelial-mesenchymal transition proteins, and obtained experimental evidence for Snail1 importance in the regulation of cell proliferation. In general, the results obtained in this study demonstrate involvement of PAK1 and Snail1 in the formation of estrogen-independent phenotype of breast cancer cells showing the potential role of both proteins as markers of hormone resistance of breast tumors.
authors.forename: E A
authors.initials: EA
authors.lastname: Avilova
authors.forename: O E
authors.initials: OE
authors.lastname: Andreeva
authors.forename: V A
authors.initials: VA
authors.lastname: Shatskaia
authors.forename: M A
authors.initials: MA
authors.lastname: Krasil'nikov
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D013629:Tamoxifen; D004958:Estradiol; D008156:Luciferases; C515903:PAK1 protein, human; D054462:p21-Activated Kinases
keywords: PAK1; Snail1; breast cancer; estrogen receptors; resistance