A New Anti-Era36 scFv to diagnose the Tamoxifen Resistant Breast Cancer

سال انتشار: 1396
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 569

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شناسه ملی سند علمی:

IPMCMED02_164

تاریخ نمایه سازی: 29 فروردین 1397

چکیده مقاله:

The estrogen receptor α has been identified in 1966, which has then led to the use of anti-estrogenic molecules in the treatment of breast cancer. Numerous studies also revealed a new cytoplasmic and membrane localized variant of ERα, named ERα-36, in breast tumor samples which does not process a complete ligand-binding domain, so that it is believed that this new variant can mediate estrogen non-genomic signaling through the rapid and transient phosphorylation of MAPK other than classical ERα ligands. ERα-36 is a potential therapeutic target because Tamoxifen can’t block ERα-36 mediated membrane-initiated estrogen signaling pathways, instead it stimulates cell growth. So targeting ERα-36 may have therapeutic results in tamoxifen resistance.Materials and Methods: For targeting receptor, an expression cassette designed. VH and VL domains are linked with the 16 amino acids linker. Signal sequence added to the beginning (N terminus) of sequence for secretion of native protein. Then considering rare codon expression cassette optimized using optimizer online software to obtain favor codon in bacterial host. Result Expression cassette formed the anti ERα-36 scFv construct which cloned and expressed in bacterial hosts. This fragment is able to aim epitope of ERα-36 as an antigen.Conclusion: Taken altogether, these observations help to conclude on the broader and more diverse ligand bonding spectrum of ERα-36 in addition to its potential for playing an independent role and being an important marker for diagnostic and therapeutic targeting. Now the new constructed scfv may target the alpha Estrogen Receptors in order to recognize the subtype of the tumor more specifically, also the sensitivity of the tumor cells to the Tamoxifen now can be predicted by this scFv monoclonal antibody in order to Choose the appropriate treatment for the patient which may lead in personalized medicine.

نویسندگان

Termeh Ghorbanian Bolouri

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Leila Farahmand

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Sepideh Mansouri

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

Shima Moradi Kalbolandi

Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.