title: HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression.
abstract: There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumour progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor β-catenin in immortalized human mammary epithelial and carcinoma cells. We found HSF1 to be involved in regulating the translation of β-catenin, by investigating effects of gain and loss of HSF1 on this protein. Interestingly, although HSF1 is a potent transcription factor, it was not directly involved in regulating levels of β-catenin mRNA. Instead, our data suggest a complex role in translational regulation. HSF1 was shown to regulate levels of the RNA-binding protein HuR that controlled β-catenin translation. An extra complexity was added to this scenario when it was shown that the long non-coding RNA molecule lincRNA-p21, known to be involved in β-catenin mRNA (CTNNB1) translational regulation, was controlled by HSF1 repression. We have shown previously that HSF1 was positively regulated through phosphorylation by mammalian target of rapamycin (mTOR) kinase on a key residue, serine 326, essential for transcriptional activity. In this study, we found that mTOR knockdown not only decreased HSF1-S326 phosphorylation in mammary cells, but also decreased β-catenin expression through a mechanism requiring HuR. Our data point to a complex role for HSF1 in the regulation of HuR and β-catenin expression that may be significant in mammary carcinogenesis.
authors: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02215.
authors: Shiuh-Dih
authors: SD
authors: Chou
authors: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02215.
authors: Ayesha
authors: A
authors: Murshid
authors: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02215.
authors: Takanori
authors: T
authors: Eguchi
authors: Boston University Medical Center, Boston, MA02215.
authors: Jianlin
authors: J
authors: Gong
authors: Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02215.
authors: Stuart K
authors: SK
authors: Calderwood
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D000067780:ELAV-Like Protein 1; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000076249:Heat Shock Transcription Factors; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; D051176:beta Catenin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases