Comparison of BRCA1 expression between triple-negative and luminal breast tumors

Background: Previous studies have suggested that BRCA1 dysregulation has been shown to have a role in triplenegative phenotypic manifestation. However, differences of BRCA1 expression, as a tumor suppressor gene, have rarely been investigated between luminal and triple-negative breast tumors. Therefore, the present study attempted to compare the BRCA1 expression in triple-negative with luminal breast tumors and its association with the clinicopathologic characteristics of patients

Methods: BRCA1 expression was evaluated by real-time PCR in 26 triple-negative and 27 luminal breast tumors

Results: The results revealed that there is a high frequency of BRCA1 underexpression in both triple-negative and luminal breast tumors. The BRCA1 underexpression was related to young age at diagnosis, lymph node involvement, and grade III tumors

Conclusion: The observations suggest that decreased BRCA1 expression, regardless of tumor subtype, has a general role in breast malignancy and associated with poor prognostic features in breast tumors

association between PARP1 and LIG3 expression levels and chromosomal translocations in acute myeloid leukemia patients

Objective: Chromosomal translocations are among the most common mutational events in cancer development, especially in hematologic malignancies. However, the precise molecular mechanism of these events is still not clear. It has been recently shown that alternative non-homologous end-joining [alt-NHEJ], a newly described pathway for double-stranded DNA break repair, mediates the formation of chromosomal translocations. Here, we examined the expression levels of the main components of alt-NHEJ [PARP1 and LIG3] in acute myeloid leukemia [AML] patients and assessed their potential correlation with the formation of chromosomal translocations

Materials and Methods: This experimental study used reverse transcription-quantitative polymerase chain reaction [RT- qPCR] to quantify the expression levels of PARP1 and LIG3 at the transcript level in AML patients [n=78] and healthy individuals [n=19]

Results: PARP1 was the only gene overexpressed in the AML group when compared with healthy individuals [P=0.0004], especially in the poor prognosis sub-group. Both genes were, however, found to be up-regulated in AML patients with chromosomal translocations [P=0.04 and 0.0004 respectively]. Moreover, patients with one isolated translocation showed an over-expression of only LIG3 [P=0.005], whereas those with two or more translocations over-expressed both LIG3 [P=0.002] and PARP1 [P=0.02]

Conclusion: The significant correlations observed between PARP1 and LIG3 expression and the rate of chromosomal translocations in AML patients provides a molecular context for further studies to investigate the causality of this association

Effects of maternal isocaloric diet containing different amounts of soy oil and extra virgin olive oil on weight, serum glucose, and lipid profile of female mice offspring

Background: Health status of offspring is programmed by maternal diet throughout gestation and lactation. The present study investigates the lasting effects of maternal supplementation with different amounts of soy oil or extra virgin olive oil [EVOO] on weight and biochemical parameters during gestation and lactation of female mice offspring

Methods: Eight weeks old female C57BL/6 mice [n=40] were assigned through simple randomization into four isocaloric dietary groups [16% of calories as soy oil [LSO] or EVOO [LOO] and 45% of calories as soy oil [HSO] or EVOO [HOO]] during three weeks of gestation and lactation. After weaning [at 3 weeks], all offspring received a diet containing 16% of calories as soy oil and were sacrificed at 6 weeks. Two-way ANOVA was used to adjust for confounding variables and repeated measures test for weight gain trend. Statistical analyses were performed with the IBM SPSS package

Results: At birth and adolescence, the weight of offspring was significantly higher in the soy oil than the olive oil groups [P<0.001 and P<0.001, respectively]. Adolescence weight was significantly higher in the offspring born to mothers fed with 16% oil than those with 45% oil [P=0.001]. Serum glucose, triglyceride and total cholesterol were significantly higher in the LSO than LOO [P<0.001, P<0.001 and P<0.001], LSO than HSO [P<0.001, P=0.03 and P<0.001], and LOO than HOO [P<0.001, P<0.001 and P<0.001] dietary groups, respectively. Serum triglyceride and total cholesterol were significantly higher in the offspring of HSO than HOO fed mothers [P<0.001 and P<0.001, respectively]

Conclusion: A maternal diet containing EVOO has better effects on birth weight, as well as weight and serum biochemical parameters in offspring at adolescence

[Expression of multiple cancer/ testis genes in 32 breast cancer tumor samples]

Cancer/testis genes [CT-genes] are a family gene which only express in normal testis tissue; some of them are randomly expressed in some types of cancers. The aim of this study was to evaluate the frequency of expression of CT-genes in the patients with breast cancer. Thirty two breast cancer tissue samples were prepared. Expression of NY-ESO-1 1a, NY-ESO-1 1b, SCP1, SSX-2 and MAGE-3 genes, as well as GAPDH [internal control], were studied by multiplex RT-PCR method. Three [9%] of 32 tumor samples expressed mRNA of NY-ESO-1 1a, while six [19%] of 32 tumor samples expressed mRNA of NY-ESO-1 1b. Seven [22%] and two [6%] of 32 tumor samples expressed mRNA of SCP1 and mRNA of MAGE3, respectively. Overall, Thirteen [41%] samples expressed one of the studied genes. NY-ESO-1 and SCP1 genes had the highest frequency of expression of mRNA. It is suggested that more number of breast cancer tumor samples should be examined to evaluate expression of CT-genes. SCP1 and NY-ESO-1 proteins may promote future breast cancer immunotherapy

Promoter hypermethylation of estrogen receptor alpha gene is correlated to estrogen receptor negativity in Iranian patients with sporadic breast cancer

Breast Cancer is the most common cancer in Iranian women. Breast tumors are classified based on the estrogen receptor alpha [ER alpha] expression status into ER negative and ER positive tumors. ER negative tumors tend to have worse prognosis and less likely to respond to endocrine therapy. Aberrant methylation of gene promoter is one of the mechanisms for gene silencing in breast tumors. Because of its reversible nature, promoter methylation is a good target for new therapeutic strategies. We aimed to evaluate the frequency of this epigenetic event in ER alpha gene and its association to clinicopathological features in Iranian breast cancer patients. In this case control study the patient series consisted of 100 sporadic primary breast cancer cases [51 ER negative and 49 ER positive tumors]. None of the participants had chemo or radiotherapy before surgery. In breast tumors ER alpha promoter methylation were assessed with methylation specific polymerase chain reaction [MSP]. Data was collected on clinicopathological features of the patients. Correlation between ER alpha methylation and clinicopathological characteristics of the patients was investigated by Pearson Chi-Square and Fisher's exact test. ER alpha methylation was detected in 98% of ER negative and 65% of ER positive breast tumors. A strong correlation was found between ER alpha methylation and ER negativity in tumors [p<0.0001]. Also, ER alpha methylation has associated to progesterone receptor negativity [p<0.008] and double receptor negative status [p<0.0001] in breast tumors. ER alpha methylation occurs with high frequency in the breast tumors of Iranian breast cancer patients and may play a considerable role in pathogenesis of ER alpha negative tumors as a poor prognosis and more aggressive category. The reversible nature of DNA methylation may provide new therapeutic possibilities in ER negative breast tumors

[Study of the association between estrogen receptor alpha gene expression in the levels of RNA and protein in primary breast tumors]

Estrogen receptor alpha protein status is determined by routine immunohistochemistry analysis in all malignant breast tumors. This assay has its limitations. RNA based techniques are potential complements for immunohistochemistry but it must be noticed that gene silencing may occur at different levels from RNA to protein. The aim of this study was the comparison of the results from these two assays and characterizing the tumors subgroup in which gene expression occurs at RNA level but the target protein is absent. 92 primary breast tumors including their clinical and IHC results were collected before treatment. Estrogen receptor gene expression of tumors was studied by Reverse Transcription Polymerase Chain Reaction [RT PCR]. In this assay, GAPDH was used as a reference gene. 36.6% of tumors with negative estrogen receptor protein showed gene expression at mRNA level. In this subgroup most of the patient were older than 50 years and in stages 3 or 4 of breast cancer and had poor prognosis according to Nottingham prognostic index. Most cases of the perineural invasion have been seen in this subgroup. It seems that RT-PCR assay would enable us to recognize a subgroup of breast tumors with poor prognosis which expresses RNA but not protein

[Epigenetic application in the breast cancer]

With 1 million new cases causing 375000 deaths worldwide per year, breast cancer is the leading cause of cancer death in women in both developing and developed countries. Recent findings indicate epigenetic modifications as key factors in breast carcinogenesis. Epigenetic refers to the cellular information of transcription memory which is transmitted through cell divisions but is not sequence based. Epigenetic is the connecting circle of the genotype and the environment. Which connect the inheritable gene transcription pattern and phenotype of a cell. DNA promoter methylation and chromatin remodeling are two main mechanisms of epigenetic modifications which are emerging as targets for breast cancer detection, prognosis and treatment. Because of their potential for reversal, epigenetic alterations are considered to be promising in caner treatment and epidrug production. Therapeutics that target methylation and histone modifications in breast cancer already exist. Advances in epidrugs are likely to play important role in future of cancer treatment