التفاصيل البيبلوغرافية
| العنوان: |
Functional Significance of the Novel H-RAS Gene Mutation M72I in a Patient with Medullary Thyroid Cancer. |
| المؤلفون: |
Barollo, S., Pezzani, R., Cristiani, A., Bertazza, L., Rubin, B., Bulfone, A., Pelizzo, M. R., Torresan, F., Mantero, F., Pennelli, G., Moro, S., Mian, C. |
| المصدر: |
Experimental & Clinical Endocrinology & Diabetes; Sep2013, Vol. 121 Issue 9, p546-550, 5p |
| مصطلحات موضوعية: |
MEDULLARY thyroid carcinoma, THYROID cancer patients, SOMATIC mutation, IMMUNOGLOBULINS, CARCINOGENESIS, WESTERN immunoblotting |
| مستخلص: |
Medullary thyroid cancer (MTC) accounts for around 5-10 % of all thyroid cancers. Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones. This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance. Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS , 1 with the Q61R mutation in H-RAS , 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I. Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding . Results of molecular dynamics were consistent with Western blot experiments. The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. This work underscores the importance of studying genetic alterations that may lead to carcinogenesis. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
