BRCA1 is a nuclear phosphoprotein that plays a key role in many cell functions, including DNA repair, control of transcription, recombination and cell cycle homeostasis. Inherited missense mutations in the BRCA1 gene may predispose to breast and ovarian cancer, but the molecular mechanisms underlying BRCA1-induced tumorigenesis are still to be elucidated. Functional studies performed so far have contributed to the characterization of several single-nucleotide variants, mostly located at the BRCT domain, but very little is known about modifications in the protein pattern occurring in cells carrying these mutations. To shed more light in the molecular events triggered by missense mutations affecting breast cancer susceptibility genes, we have analyzed the whole cell proteome of stably transfected HeLa cell lines bearing three distinct single aminoacid changes in the BRCA1 protein (Ser1841Asn, Met1775Arg and Trp1837Arg) by means of liquid chromatography coupled to tandem-mass spectrometry. The results show that the Met1775Arg and the Trp1837Arg do not produce significant changes in the proteomic pattern compared to cells transfected with the wild-type BRCA1 cDNA. On the other hand, a different profile is detected in the BRCA1 Ser1841Asn-bearing cell line. In this particular subset, our attention has been focused on two proteins - the tumor protein D52 (TD52) and the folate receptor alpha (FOL1) - whose expression has been already reported to be upregulated in breast cancer, as well as in other tumors. Our findings indicate that Ser1841Asn BRCA1 mutation is able to activate specific protein pathways that are not triggered by other single aminoacid changes and pinpoint to the role TD52 and FOL1 as potential markers in breast cancer patients carrying this particular BRCA1 gene alteration.

Specific changes in the proteomic pattern produced by the BRCA1-Ser1841Asn missense mutation / T. Crugliano, B. Quaresima, M. Gaspari, M.C. Faniello, F. Romeo, F. Baudi, G. Cuda, F. Costanzo, S. Venuta. - In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. - ISSN 1357-2725. - 39:1(2007), pp. 220-226. [10.1016/j.biocel.2006.08.005]

Specific changes in the proteomic pattern produced by the BRCA1-Ser1841Asn missense mutation

F. Romeo;
2007

Abstract

BRCA1 is a nuclear phosphoprotein that plays a key role in many cell functions, including DNA repair, control of transcription, recombination and cell cycle homeostasis. Inherited missense mutations in the BRCA1 gene may predispose to breast and ovarian cancer, but the molecular mechanisms underlying BRCA1-induced tumorigenesis are still to be elucidated. Functional studies performed so far have contributed to the characterization of several single-nucleotide variants, mostly located at the BRCT domain, but very little is known about modifications in the protein pattern occurring in cells carrying these mutations. To shed more light in the molecular events triggered by missense mutations affecting breast cancer susceptibility genes, we have analyzed the whole cell proteome of stably transfected HeLa cell lines bearing three distinct single aminoacid changes in the BRCA1 protein (Ser1841Asn, Met1775Arg and Trp1837Arg) by means of liquid chromatography coupled to tandem-mass spectrometry. The results show that the Met1775Arg and the Trp1837Arg do not produce significant changes in the proteomic pattern compared to cells transfected with the wild-type BRCA1 cDNA. On the other hand, a different profile is detected in the BRCA1 Ser1841Asn-bearing cell line. In this particular subset, our attention has been focused on two proteins - the tumor protein D52 (TD52) and the folate receptor alpha (FOL1) - whose expression has been already reported to be upregulated in breast cancer, as well as in other tumors. Our findings indicate that Ser1841Asn BRCA1 mutation is able to activate specific protein pathways that are not triggered by other single aminoacid changes and pinpoint to the role TD52 and FOL1 as potential markers in breast cancer patients carrying this particular BRCA1 gene alteration.
BRCA1; Breast cancer; FOL1; Proteomics; TD52; Amino Acid Substitution; BRCA1 Protein; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; Female; Folate Receptors, GPI-Anchored; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; HeLa Cells; Humans; Neoplasm Proteins; Ovarian Neoplasms; Proteomics; Receptors, Cell Surface; Mutation, Missense
Settore BIO/10 - Biochimica
Settore BIO/11 - Biologia Molecolare
Settore MED/04 - Patologia Generale
2007
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S1357272506002378-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 219.03 kB
Formato Adobe PDF
219.03 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/854947
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact