Potential Candidate Genes for Therapeutic Targeting in Chronic Myeloid Leukemia: A Pilot Study.

BACKGROUND: Chronic myeloid leukemia (CML) is a prevalent hematological malignancy known for the presence of the Philadelphia chromosome and activation of the BCR-Abl kinase activity. Although tyrosine kinase inhibitors are widely used as the standard treatment, resistance remains a concern among certain patients. This study aimed to investigate the gene expression profile of a group of CML patients in comparison to a control group in order to identify novel candidate genes associated with the disease. METHODS: Whole transcriptome sequencing was performed, and gene expression levels were validated using quantitative real-time PCR. Additionally, single nucleotide and insertion/deletion variants were analyzed in the selected candidate genes among 10 CML patients and 4 healthy control subjects. RESULTS: Analysis revealed a set of differentially expressed genes, whose up- or downregulation was further confirmed by qRT-PCR. Among the upregulated genes in the patient group were ribosomal protein like (RPL) members, specifically RPL9, RPL34, RPL36A, and RPL39, while downregulation was observed in CCDC170, LDB1, and SBF1 compared to the healthy subjects. Furthermore, gene variant studies identified novel genetic changes in these candidate genes, suggesting potential clinical significance in CML. CONCLUSIONS: This study highlights RPL9, RPL34, RPL36A, RPL39, CCDC170, LDB1, and SBF1 as potential targets in CML. Additionally, it underscores the importance of investigating these genes and their variants in larger cohort studies to assess their clinical significance in CML patients.

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study.

Background: Cardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn't been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state. Methods: This is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls). Results: sP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases. Conclusion: Our study supports the previous researches' results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.

Whole-transcriptome bioinformatics revealed HTRA3, KRT8, KRT17, and RHEX as novel targets in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is characterised by heterogeneous genomic signatures that vary among different patient groups. Hence, the current study aims to conduct a whole transcriptome analysis of a female patient with AML and a family history of the disease at the time of diagnosis. Genetic profiling has a useful impact on clinical management and treatment success of the disease as the complex genetic landscape of AML and differential responses to treatment might indicate inadequate therapeutic targeting. A 37 year old female patient with AML was admitted to the hospital complaining of general fatigue arthralgia and chest pain. AML diagnosis was confirmed by complete blood count and blood smears before being confirmed by cytogenetic analysis. Herein, we conducted whole-transcriptome sequencing analysis to assess differential gene expression profiles in patients and healthy control subjects. In addition, single nucleotide polymorphism/insertion-deletion analyses (SNP/INDEL) were performed to investigate gene variants in the present case. The results revealed a remarkable differential gene expression profile in AML compared to the corresponding control at the time of diagnosis, indicating that HTRA3, KRT8, KRT17, and RHEX are potential novel therapeutic targets. Additionally, a number of novel gene variants were also reported in the current study, as concluded from the SNP/INDEL analysis, which might be associated with disease risk assessment and probably affect prognosis. These genes and their new variants might be worth reporting to the scientific community for further exploration of AML.

Phenotypic and Genotypic Signatures of VWF Exon 18 in Eastern Saudi Patients Previously Diagnosed with Type 1 von Willebrand Disease.

Introduction: von Willebrand disease (VWD) is the most prevalent bleeding disease, which is associated with either low levels of von Willebrand factor (VWF) or abnormality in its structure. Three types of the disease have been described; type 1 (VWD1) and 3 (VWD3) are caused by deficiency of VWF and type 2 (VWD2) is caused by production of defective VWF. The aim of the current study was to characterize gene variants of VWF gene; exon 18 in particular, in a cohort of Saudi families as well as healthy control subjects. Methods: A total of 19 families comprising 60 subjects of type 1 VWD were enrolled in the study. Participants were divided into 22 index cases, 21 affected family members and 17 unaffected family members ranging in age from 6 to 70 years. Blood samples were collected from all participants to measure activated partial thromboplastin time test (APTT), von Willebrand antigen level (VWF:Ag), Factor VIII activity (FVIII:C) and ristocetin cofactor activity (VWF:RCo), platelet count, determining the ABO blood group and for genetic analysis by Sanger sequencing. Results: The results indicated that VWD1 patients have lower levels of VWF and factor VIII than the non-affected family members and the control subjects. In addition, five gene variants were reported in VWF exon 18; of these, c.2365A>G and c.2385T>C were more common in the control group and might be protective from VWD. Discussion: In conclusion, VWF levels are influenced by blood group, and there was no association between variants in exon 18 of VWF gene reported in all groups and the disease status; however, blood group analysis and genome-wide genotyping could help to highlight high-risk groups and improve clinical management of VWD.

Incidence and assessment of demography-related risk factors associated with pulmonary tuberculosis in Saudi Arabia: A retrospective analysis.

Background & Objectives: Tuberculosis (TB) is a public health challenge and is endemic in many countries including Saudi Arabia. The disease is a major health concern in the Kingdom because of its dynamic population as resident expatriates are mainly from high TB burdened countries and the mass influx of pilgrims every year in peak seasons for Umrah and Hajj. The objective of the current study was to evaluate pulmonary TB incidence rates and conclude the potential high-risk patients to highlight the burdened regions in Saudi Arabia for the health authorities, which could help to establish policies of infection control as necessary. Methods: We retrospectively investigated the incidence of pulmonary TB data reported by the ministry of health (MOH) in 2018. We analyzed pulmonary TB incidence data by nationality, age, gender, and region using Chi-square test to identify demography-related risk factors associated with pulmonary TB and its significance. Results: The results indicated that the incidence of pulmonary TB was significantly higher in males than in females in both Saudi and non-Saudi nationals; the number of cases was particularly high in major cities. Also, infections were mainly associated with certain age groups that were different between the Saudi and non-Saudi nationals. Conclusion: TB control seems to be facing some challenges in several regions of the Kingdom, particularly major cities. National TB Control Program (NTP) needs to continually evaluate official data to spot high risk groups and factors associated with increased incidence. This will help to improve TB control strategies to contain the disease and approaches its eradication.

Oral Intragastric DMBA Administration Induces Acute Lymphocytic Leukemia and Other Tumors in Male Wistar Rats.

BACKGROUND: Animal models of blood cancer are important tools to study these malignancies and also screen for novel therapeutic agents. Evidence from past research on the carcinogenic properties of 7,12-dimethylbenz[a]-anthracene (DMBA) was provided by a handful of studies. However, recent literature on DMBA carcinogenic activity and the underlying mechanisms is scarce. OBJECTIVE: The aim of this study was to develop a chemical model of leukemia using DMBA. Male Wistar rats (6 weeks old) were administered 1.5 mg of DMBA dissolved in sesame oil in biweekly doses using oral intragastric intubation. MATERIALS AND METHODS: Frequent complete blood counts and blood smear morphology assessment were used to assess the development of leukemia, while gross pathology and histopathology staining were used to evaluate malignancy development. RESULTS: The results showed that only 4% of rats developed acute lymphocytic leukemia. Interestingly, 36% of the rats developed tumors (parotid tumors [24%] and fibrosarcomas [12%]). CONCLUSION: These results suggest the pleiotropic potential of DMBA in the induction of multiple types of malignancies, including leukemia. This could be used as a model to validate therapeutic targets for leukemia and other induced malignancies.

ADAMTS14, ARHGAP22, and EPDR1 as potential novel targets in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a blood cancer with a heterogeneous genomic landscape. This study aimed to mine bioinformatics data generated by RNA sequencing to unveil an AML case transcriptome profile and identify novel therapeutic targets and markers. In this study, we have determined the transcriptomic profile and analysed gene variants of an AML patient at the time of diagnosis and validated some genes by quantitative reverse transcriptase polymerase chain reaction. ADAMTS14, ARHGAP22, and ependymin-related protein 1 (EPDR1) were markedly upregulated compared to the corresponding control. In addition, novel exonic single-nucleotide and insertion/deletion variants were identified in these genes. Hence, ADAMTS14, ARHGAP22, and EPDR1 can be proposed as potential novel targets in AML, and their exact roles should be further explored.

A 20-year retrospective clinical analysis of Candida infections in tertiary centre: Single-center experience.

INTRODUCTION: Fungal infections have risen exponentially in the last decade. In fact, candidiasis has become the most frequent type of hospital acquired infection especially in patients receiving treatment for chronic and terminal illnesses in a hospital. A retrospective analysis for a period of twenty year was undertaken to analyze the incidence rate of candidiasis, especially of Candida species, patients treated in a tertiary care center. MATERIALS AND METHODS: Clinical data was collected from samples of patients who were receiving tertiary care were presenting with clinically suspected fungal infections. Direct microscopy with 10% potassium hydroxide was done to visualize the presence of fungal elements, and Gram staining was done for any suspected yeast infection. The samples were inoculated on Sabouraud's Dextrose Agar and kept at 22 °C. RESULTS: A total of 1256 samples with presumed fungal etiology were included in the study. The maximum number of fungal infections were present in elderly (70-79 years age). Females (53.8%) were more affected (45.5%). 21% isolates were identified as yeast but belonged to non-Candida fungi. Among Candida species, Candida albicans was the most dominant species (58.3%) followed by Candida glabrata (6.4%). The year-round data of fungal cases showed that the highest incident of Candida albicans infection were in January with a mean value of 3.80, while the lowest infections were reported in June, with prevalence of 2.32 of C. albicans. The twenty-year data analysis showed that the years 2001 and 2000 showed the highest incidents of C. albicans, with a mean prevalence of 7.50 and 6.83, respectively. Specimen vs fungal prevalence data showed that 38% of the C. albicans were isolated from body aspirate specimens, followed by 26% from swab specimens. CONCLUSION: The high prevalence of Candida spp. in the present study suggests increased susceptibility of patients with critical or chronic illnesses to fungal infections.

Comparative cross-sectional assessment of knowledge, attitude and practice among university students and employees towards the use of the microbiology laboratory equipment.

Background: Continuous evaluation of students and employee's knowledge and attitude in clinical laboratories is mandatory to ensure a high level of competency, proper practice and to assess the need for training, which shall be reflected on the quality of laboratory results. The aim of the present study was to evaluate the knowledge, attitude, and practice in microbiology laboratories among employees (at King Fahd Hospital of the University) and clinical laboratory students (at Imam Abdulrahman Bin Faisal University)    Methods: This was a cross-sectional survey of 30 2 nd year students, 26 3 rd year students, 24 4 th year students in the Clinical Laboratory Sciences department, and 30 employees. Participants completed a survey comprising 30 questions to assess their knowledge and attitude towards the use of equipment and practice in the microbiology laboratory. Results: The results indicated that there was no significant difference between the average scores of all levels of students regarding their knowledge (p = 0.85, 0.999, and 0.869), attitude (p = 0.883, 0.996, 0.853), and practice (p=0.633, 0.325, 0.858) in the microbiology laboratory. Employees scores (knowledge;5.03±2.646, attitude; 12.03±4.89, and practice; 7.7±6.11) were quite poor, as indicated by the lower average results than that of students (knowledge; 5.65±3.08, attitude; 13.25±5.33, and practice; 13.46±5.7). Conclusions: It is concluded that the knowledge, attitude, and practice of students and employees in the microbiology laboratory needs to be meticulously monitored and improved to ensure high achievement of learning outcomes and better overall performance in the laboratory. This may be achieved through using frequent quizzes and continuous education programs.

RNA sequencing identified novel target genes for Adansonia digitata in breast and colon cancer cells.

Adansonia digitata exhibits numerous beneficial effects. In the current study, we investigated the anti-cancer effects of four different extracts of A. digitata (polar and non-polar extracts of fruit powder and fibers) on the proliferation of human colon cancer (HCT116), human breast cancer (MCF-7), and human ovarian cancer (OVCAR-3 and OVCAR-4) cell lines. RNA sequencing revealed the influence of the effective A. digitata fraction on the gene expression profiles of responsive cells. The results indicated that only the polar extract of the A. digitata fibers exhibited anti-proliferative activities against HCT116 and MCF-7 cells, but not ovarian cancer cells. Moreover, the polar extract of the fibers resulted in the modulation of the expression of multiple genes in HCT116 and MCF-7 cells. We propose that casein kinase 2 alpha 3 (CSNK2A3) is a novel casein kinase 2 (CSNK2) isoform in HCT116 cells and report, for the first time, the potential involvement of FYVE, RhoGEF, and PH domain-containing 3 (FGD3) in colon cancer. Together, these findings provide evidence supporting the anti-cancer potential of the polar extract of A. digitata fibers in this experimental model of breast and colon cancers.

RNA sequencing-based identification of potential targets in acute myeloid leukemia: A case report.

Acute myeloid leukemia (AML) refers to heterogenous types of blood cancer which possess a complicated genomic landscape, and multiple novel mutational alterations are frequently being reported. Herein, a case report of a 37-year old AML patient is presented, who was diagnosed following laboratory investigation after admission. The patient had thrombocytopenia, and three consecutive blast counts of 40, 30 and 41%, respectively. A blood sample was collected for whole-genome RNA sequencing to understand the transcriptomic profile at the time of diagnosis and compared with a matched female control. Gene expression was quantified using the RSEM software package. Bioinformatics analysis revealed a significant number of differentially expressed genes in the patient, suggesting a marked change in the transcriptomic landscape in this patient. By mining the bioinformatics data and screening the highly expressed genes with ≥80% probability of gene expression, four novel genes were highlighted that may serve as potential future targets in AML patients; Rh associated glycoprotein, succinate receptor 1, transmembrane-4 L-six family member-1 and ADGRA3, although further validation of their value is required.

AMPK Activation of Apoptotic Markers in Human Breast Cancer Cell Lines with Different p53 Backgrounds: MCF-7, MDA-MB-231 and T47D Cells.

BACKGROUND: Downregulation of AMPK has been established as a major contributor to carcinogenesis in many types of human cancer. We sought to investigate the influence of activated AMPK on apoptotic markers in human breast cancer cells differing in their p53 status, as well as estrogen receptor status (MCF-7 (p53+ and ER+), MDA-MB-231 (p53 mutant and ER-) and T47D (p53 mutant and ER+)). METHODS: We examined the effect of AICAR-activated AMPK on PARP cleavage, Bax redistribution, the involvement of intrinsic and extrinsic pathways of apoptosis using selective caspase inhibitors and cell cycle progression and p21 levels. RESULTS: PARP cleavage occurred to a greater extent in MCF-7 and MDA-MB-231 cells, whereas Bax translocation was slower in MDA-MB-231 cells. Although there were quantitative differences in the effect of caspase inhibitors, it was clear that AMPK activation predominately affected the intrinsic pathway of apoptosis. Although, p21 was increased in all 3 cell types, there were quantitative and time differences. Apoptosis, as measured by fluorimetry, was increased in all three cell types. CONCLUSION: The impact of AMPK activation was cell type dependent resulting in differential activation of apoptotic markers, confirming that the genetic background of breast cancer may have an influence on the mode of action of AMPK. Thus, different anti-tumour mechanisms may be elicited depending on the cellular genotype.

Staurosporine alleviates cisplatin chemoresistance in human cancer cell models by suppressing the induction of SQSTM1/p62.

Cancer is one of the leading causes of mortality worldwide. Platinum­based chemotherapeutic agents such as cisplatin are the first line of treatment for many types of cancers. However, the development of cisplatin resistance after prolonged treatment is a common cause of cancer recurrence. In the present study, we investigated an approach designed to overcome resistance to cisplatin involving co­treatment with a second chemotherapeutic agent, staurosporine, and examined the role of sequestosome 1 (SQSTM1/p62) in enhancing cellular sensitivity to cisplatin. We utilized experimental models of three different cancers comprising cell lines derived from colon, breast, and ovarian tumors and investigated cell proliferation, morphology and p62 levels after treatment with cisplatin, staurosporine, or a combination of the two. Western blot analysis showed that cisplatin treatment resulted in elevation of p62 levels when compared to the corresponding control cells. Conversely, treatment with staurosporine resulted in a marked reduction in p62 levels in all three cell types and abrogated the cisplatin­induced upregulation of p62. These results suggest that staurosporine could sensitize cancer cells to cisplatin via a mechanism involving downregulation of p62.

Interferon regulatory factor 1 inactivation in human cancer.

Interferon regulatory factors (IRFs) are a group of closely related proteins collectively referred to as the IRF family. Members of this family were originally recognized for their roles in inflammatory responses; however, recent research has suggested that they are also involved in tumor biology. This review focusses on current knowledge of the roles of IRF-1 and IRF-2 in human cancer, with particular attention paid to the impact of IRF-1 inactivation. The different mechanisms underlying IRF-1 inactivation and their implications for human cancers and the potential importance of IRF-1 in immunotherapy are also summarized.

Novel IRF-1 Mutations in a Small Cohort of Leukaemia Patients From Saudi Arabia

Involvement of the Interferon Regulatory Factor 1 (IRF-1) gene in regulation of cell differentiation and proliferation made it a potential target in cancer research. IRF-1 acts as a tumor suppressor gene, and is inactivated in chronic (CML) and non-chronic myelogenous leukemia (non-CML). In the light of numerous reports on genetic changes in the noncoding region of the IRF-1 gene, this study aimed to explore possible genomic changes in coding and non-coding regions of IRF-1 in a random sample of leukemic Saudi patients, in order to obtain insights into potential impact of genetic changes on clinicopathological characteristics. Patients were classified into two major leukemia subtypes: CML (8 cases; 36.4%) and non-CML (14 cases; 63.6%). Sequencing results revealed two novel mutations in the coding area of the IRF-1 gene likely to influence the IRF-1/DNA binding affinity. In addition, three mutational sites in the noncoding region between exon 5&6 (8985(T>G), 8,990(T>G) and 8995(A>G) were identified. In conclusion, a larger representative study might help provide better understanding of the possible contribution of the identified genetic changes in IRF-1 to disease prognosis and outcomes in leukemic patients.

Developmental Phases of Anticancer Screening Models.

The development of new screening models for cancer therapy is indispensable for the improvement of cancer treatment, and for the creation of alternative possibilities in the field of chemotherapy. Screening models are routinely used to reduce the cost and resources involved in anticancer drug development. The value of any screening model will ultimately be ascertained by its ability to reliably predict the clinical response. Traditional in vivo screening models have been replaced with cell-based screening assays, and these cell-based models are under constant development to better mimic in vivo conditions. In this review, the developmental phases of anticancer screening models are discussed and exemplified, including the two-dimensional, threedimensional, cancer stem cell, and non-mammalian screening models. In addition, the use of new virtual screening tools as a model for anticancer drug development is highlighted.

The anti-oncogenic influence of ellagic acid on colon cancer cells in leptin-enriched microenvironment.

Ellagic acid (EA) has been proposed as a promising candidate for therapeutic use in colon cancer. Investigation of the effectiveness of EA in a leptin-enriched model might have been given a little interest. Here in, we investigated the anti-tumor effect of EA in the presence of leptin to reflect on therapeutic use of EA in obesity-linked colon cancer. Proven effective in leptin-enriched microenvironment, EA inhibited cell proliferation of HCT-116 and CaCo-2 cell lines, modulated cell cycle, translocated Bax to the mitochondrial fraction of cells, activated caspase-8, and reduced PCNA expression. The current study findings cast a beam of light on the potential therapeutic use of EA in obesity-related colon carcinogenesis.

Impact of Cellular Genetic Make-up on Colorectal Cancer Cell Lines Response to Ellagic Acid: Implications of Small Interfering RNA.

BACKGROUND: K-Ras activation is an early event in colorectal carcinogenesis and associated mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent. PURPOSE: To evaluate the impact of cellular genetic make- up of two colon cancer cell lines with different genetic backgrounds, HCT-116 (K-Ras-/p53+) and Caco-2 (K-Ras+/ p53-), on response to potential anti-tumour effects of EA. In addition, the influence of K-Ras silencing in HCT- 116 cells was investigated. MATERIALS AND METHODS: Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of K-Ras siRNA or incubated with ellagic acid following transfection. RESULTS: The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473) was downregulated. Moreover, EA treatment was found to (i) reduce K-Ras protein expression; (ii) in cells transfected with siRNA and co-treated with EA, pronounced anti-proliferative effects as well as depletion of p-Akt (at Thr308) were detected. CONCLUSIONS: Cellular genetic makeup (K-Ras-/p53-) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant K-Ras).

Differential crosstalk between the AMPK and PI3K/Akt pathways in breast cancer cells of differing genotypes: Leptin inhibits the effectiveness of AMPK activation.

AMP-activated protein kinase (AMPK), a sensor of cellular energy, is widely reported as a potential therapeutic target in treatment of breast and other cancers. The activated enzyme has been shown to be a promising anti-proliferative agent in breast cancer cell lines. However, little data exist on crosstalk between AMPK and the cellular survival axis of PI3K/Akt/mTOR pathway and the impact of microenvironment on cellular responses to AMPK activation. We present results which show differential crosstalk between AMPK and Akt, dependent on the cellular genetics of each breast cancer cell type. We also show that leptin blocks activation of AMPK and partially or completely attenuates the anti-proliferative effect of AMPK activation depending on the cell type. This suggests that leptin within the local environment might impose limitations on therapeutic usage of AMPK activators in cancer, thereby attenuating their effective use in many obese subjects.

Effects of activation of AMPK on human breast cancer cell lines with different genetic backgrounds.

Breast cancer remains a therapeutic challenge, and this has intensified the search for new drug targets. The AMP-activated protein kinase (AMPK) signalling pathway is emerging as having potential for intervention. We assessed the possible different effects of AMPK action on breast cancer cells by studying their impact on proliferation, apoptosis and the mitochondrial membrane potential in three breast cancer cell lines (MCF-7, MDA-MB-231 and T47D) differing in their p53 and estrogen receptor (ER) status. Activation of AMPK by 5-aminoimidazole carboxamide ribonucleotide (AICAR) and phenformin elicited clear anti-proliferative effects in all breast cancer cell lines, but with differences in sensitivity. However, the anti-proliferative effects were accompanied by varying responses between the different cells, with a marked cell cycle arrest effect in T47D cells and an apoptotic effect in MCF-7 and MDA-MB-231 cells. The mitochondrial apoptotic pathway was potentially involved in all cell lines. These results suggest that AMPK potentially serves as a therapeutic target in breast cancer, but one which may be dependent on the genetic background of the cancer cells.