Characterization of an interesting novel mutant strain of commercial Saccharomyces cerevisiae

The yeast strains that are resistant to high concentration of ethanol have biotechnological benefits and are suitable models for physiology and molecular genetics research fields. A novel ethanol-tolerant mutant strain, mut1, derived from the commercial Saccharomyces cerevisiae showed higher ethanol production, and also demonstrated resistance to ethanol but not to other alcohols, such as methanol, 2-propanol, and 1-butanol. To characterize mut1, the strain's resistance to other organic compounds and osmotic and cell wall stresses were examined. The growth of the mut1 strain in the presence of ethyl n-caproate and 3-methyl butyl acetate, which were metabolic derivatives of ethanol, was found to be less than the wild type. On the other hand, the growth of the mut1 strain in the presence of 50% [w/v] sucrose and 1M NaCl was similar to that of the wild type. The sensitivity to cell wall digestive enzyme, zymolyase, was also similar in both wild and mut1 strains. Finally, the mut1 strain showed resistance to homocysteine and serine but was sensitive to methionine. These results suggest that the ethanol resistance of the mut1 strain may be more related to the ethanol metabolic and signalling pathways rather than the enhanced stress resistances relating to the membrane or cell wall compositions

Pharmacogenomic profiling of the PI3K/PTEN pathway in sporadic breast cancer

Pharmacogenomics is the study of genetic variations among individuals to predict the probability that a patient will respond to single or multidrug chemotherapy. Breast cancer is one of the most common cancers among women worldwide. Treatment of breast cancer by application of biological rationales gives us the ability to match the correct pharmacology to individual tumour genetic profiles. The breast cancers exhibit multiple anomalies in phosphatidylinositol 3 kinase pathways, such as phosphatase and tensin homolog deleted on chromosome TEN loss that can be put in context of therapy with rapamycin analogues. Considering the high incidence of breast cancer in Iran, the potential role of tumor suppressor PTEN/MMAC1gene was investigated in Isfahanian breast cancer patients. In this study, PTEN was evaluated by means of polymerase chain reaction, single strand conformation polymorphism, Heteroduplex mobility assay and direct DNA sequencing in 72 breast cancer tumors for detection and characterization of mutations. According to the results of this research, nucleotide substitutions were found in 5/72 [7%] of samples. The sporadic breast cancer patient was found to be heterozygote for the p.D92N, p.C105W, p.D107N, p.A121P and p.R 130Q mutations. One novel mutation, p.D107N, was found in this study. Loss of PTEN function in breast cancer can occur either by mutation or reduction of PTEN expression in almost half of sporadic breast tumors. This rate of mutations is an important consideration for novel therapeutic in which biological efficacy is influenced by the activity of PTEN

[Mutational analysis of the PTEN/MMAC1 tumer suppressor gene in sporadic breast cancers]

PTEN [or MMAC1/TEP1] is a tumor suppressor gene that its mutations and deletions were detected in glioma, prostate, melanoma, Endometrium and breast cancers, abundantly. Most mutations occur in exon 5 that codes main domain of PTEN protein. PTEN acts as a lipid phosphate and is regulators of PI3/AKT kinase pathway. PTEN also is a protein phosphate that phosphorelates serine and threonine residues. PTEN with protein-phosphate function plays roles in regulation of several cellular pathways including MAPK. Considering the efficacy of novel drugs [like CCI-779] and therapeutic trials [like rapamycin] demonstrated for breast cancer therapy, influence by the inactivation of PTEN, and high incidence of breast cancer in Isfahan, the potential role of this gene in mammary carcinogenesis was further investigsted. 62 breast cancers were examined for mutations in PTEN/MMAC1 by means of polymerase chain reaction, single-strand conformation polymorphism, heteroduplex and sequencing. According to the results of this research, deletions/insertions and nucleotide changes were found in 2/62 [3%] and 5/62 [8%] of samples, respectively. This rate of mutations in PTEN promises efficacy of new drugs in treatment of patients with breast cancer in Isfahan