Leucine Zipper Downregulated In Cancer 1 Research Articles

Leucine Zipper Downregulated in Cancer-1 Interacts with Clathrin Adaptors to Control Epidermal Growth Factor Receptor (EGFR) Internalization and Gefitinib Response in EGFR-Mutated Non-Small Cell Lung Cancer.

The epidermal growth factor receptor (EGFR) is a common driver of non-small cell lung cancer (NSCLC). Clathrin-mediated internalization (CMI) sustains EGFR signaling. AXL is associated with resistance to EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutated (EGFRM) NSCLC. We investigated the effects of Leucine zipper downregulated in cancer-1 (LDOC1) on EGFR CMI and NSCLC treatment. Coimmunoprecipitation, double immunofluorescence staining, confocal microscopy analysis, cell surface labelling assays, and immunohistochemistry studies were conducted. We revealed that LDOC1 interacts with clathrin adaptors through binding motifs. LDOC1 depletion promotes internalization and plasma membrane recycling of EGFR in EGFRM NSCLC PC9 and HCC827 cells. Membranous and cytoplasmic EGFR decreased and increased, respectively, in LDOC1 (-) NSCLC tumors. LDOC1 depletion enhanced and sustained activation of EGFR, AXL, and HER2 and enhanced activation of HER3 in PC9 and HCC827 cells. Sensitivity to first-generation EGFR-TKIs (gefitinib and erlotinib) was significantly reduced in LDOC1-depleted PC9 and HCC827 cells. Moreover, LDOC1 downregulation was significantly associated (p < 0.001) with poor overall survival in patients with EGFRM NSCLC receiving gefitinib (n = 100). In conclusion, LDOC1 may regulate the efficacy of first-generation EGFR-TKIs by participating in the CMI of EGFR. Accordingly, LDOC1 may function as a prognostic biomarker for EGFRM NSCLC.

Leucine zipper downregulated in cancer 1 may serve as a favorable prognostic biomarker by influencing proliferation, colony formation, cell cycle, apoptosis, and migration ability in hepatocellular carcinoma.

Aims: Leucine zipper downregulated in cancer 1 (LDOC1) inhibits tumor growth in several cancers. However, the expression and function of LDOC1 in hepatocellular carcinoma (HCC) remain unknown. In this study, we aimed to investigate how LDOC1 influenced tumor progression and the biological functions of HCC. Methods: The transcription levels of LDOC1 were determined using the GEPIA and UALCAN online databases and a real-time polymerase chain reaction. Western blot and immunohistochemistry were used to validate the protein levels of LDOC1. The online Kaplan-Meier Plotter was applied for survival analysis. Then lentivirus transfection was used to construct LDOC1 exogenous overexpression cell lines. Proliferation, clone formation, cell cycle, apoptosis, and migration assays were performed with the LDOC1-upregulated Huh7 and Hep3B cell lines. The phosphorylated and total levels of AKT and mTOR were determined using a Western blot to explore the potential molecular mechanism of LDOC1. Results: In the GEPIA and UALCAN analyses, LDOC1 was lowly expressed in tumors, had high expression in normal tissue samples (p < 0.05), and negatively correlated with tumor grade progression. The down-regulation of LDOC1 in HCC was validated with real-time polymerase chain reaction, Western blot, and immunohistochemistry (all p < 0.05). LDOC1 transcription levels were negatively associated with overall, progression-free, recurrence-free, and disease-specific survival (all p < 0.05). The functional experiments suggested that the overexpression of LDOC1 contributed to increased G1 and G2 stages in Huh7, while increased G2 stage in Hep3B, and decreased cell proliferation, clone formation, and migration, as well as increased the apoptosis rate compared with the control group (all p < 0.05). Furthermore, LDOC1 up-regulation reduced the p-AKT/AKT and p-mTOR/mTOR, which indicates an inactivation of the AKT/mTOR pathway. Conclusion: The tumor-suppressor LDOC1 varied in HCC and non-HCC tissues, which can serve as a candidate prognostic biomarker. LDOC1 influenced survival by affecting proliferation, colony formation, cell cycle, apoptosis, and migration ability, which might be attributed to the AKT/mTOR inhibition in HCC.

LDOC1 is differentially expressed in thyroid cancer and display tumor-suppressive function in papillary thyroid carcinoma.

The leucine zipper downregulated in cancer 1 (LDOC1) has been proposed as a regulator of transcription and cell signaling. We have previously demonstrated that LDOC1 is differentially expressed in papillary thyroid carcinoma (PTC), this study was designed to characterize LDOC1 expression in thyroid follicle originated cancer tissues and to specifically evaluate its function in thyroid carcinogenesis. LDOC1 expression was performed in human normal thyroid and thyroid cancer. LDOC1 function was characterized, in two PTC cell lines (TPC1 and BCPAP), through the analysis of in vitro cell proliferation, apoptosis, migration, and invasion along with in vivo tumor xenograft growth. Transduced BCPAP cells were stimulated with tumor necrosis factor α, and the levels of nuclear P65, Bax, Bcl-2, c-Myc, and XIAP were assessed. A luciferase reporter assay was used to measure nuclear factor-κB (NF-κB) activity, and the functional connection between LDOC1 effect and NF-κB activity was determined using a specific NF-κB inhibitor. Our results revealed that LDOC1 was translocated from the nucleus to the cytoplasm in human thyroid cancer, and was significantly downregulated in PTC compared with normal thyroid. LDOC1 overexpression in TPC1 resulted in a significant suppression of the malignant phenotype, whereas LDOC1 ablation in BCPAP promoted this phenotype. Additional studies demonstrated that LDOC1 ablation facilitated nuclear P65 expression and NF-κB activity. NF-κB inhibition reversed the effects of LDOC1 ablation on proliferation, apoptosis, migration, and invasion. Our findings confirmed that LDOC1 is a novel therapeutic target in PTC and provides new insight into the role of LDOC1 in PTC progression, through NF-κΒ signaling suppression.

HAND2-AS1 inhibits invasion and metastasis of cervical cancer cells via microRNA-330-5p-mediated LDOC1

BackgroundCervical cancer is a serious disease with complicated pathogenesis and thus there is an urgent need to find novel targets for the treatment. Recently, long non-coding RNAs (lncRNAs) have emerged as critical factors in tumorigenesis. In this study, we aimed to investigate the mechanism of HAND2 antisense RNA 1 (HAND2-AS1) on the invasion and metastasis of cervical cancer cells.MethodsThe expression patterns of HAND2-AS1, microRNA-330-5p (miR-330-5p) and leucine zipper down-regulated in cancer 1 (LDOC1) in cervical cancer were characterized by RT-qPCR and western blot analysis. Dual luciferase reporter assay and RIP were applied to verify relationship between HAND2-AS1, miR-330-5p and LDOC1. Fluorescence in situ hybridization (FISH) was used to detect the subcellular localization of HAND2-AS1. Besides, viability, invasion and migration ability of HeLa cells were investigated by cell counting kit-8 (CCK-8) and Transwell assays respectively. Hematoxylin–eosin staining was performed for lymph node metastasis detection. In addition, the tumor growth in nude mice was evaluated.ResultsLow expression of HAND2-AS1 and LDOC1, and high expression of miR-330-5p were detected in cervical cancer tissues and cells. It was found that binding of HAND2-AS1 to miR-330-5p results in upregulation of LDOC1 expression. Also, overexpressed HAND2-AS1 and LDOC1 or down-regulated miR-330-5p inhibited expression of proliferation-associated proteins Ki-67, PCNA, migration-associated proteins N-cad and invasion-related proteins MMP-2, MMP-9 as well as lymph node metastasis. Moreover, HAND2-AS1 inhibited tumor formation and lymph node metastasis by binding to miR-330-5p in vivo.ConclusionHAND2-AS1 promotes LDOC1 expression by competitively binding to miR-330-5p and consequently inhibiting cervical cancer cell invasion and metastasis. This could facilitate development of therapeutic strategies against cervical cancer.

ABCB7 is a gatekeeper of both programmed cell death, apoptotic and non-apoptotic cell death

Abstract Background The ATP-binding cassette (ABC) transporters are superfamily proteins of cellular translocation machinery. Many ABC transporters release drugs to give multidrug resistance. However, ABC transporters existing in intracellular compartments give drug resistance by regulating biological processes, rather than direct release of drugs. The current study aimed to investigate the molecular mechanism that causes the drug resistance of the mitochondrial ABC transporters in cancer cells. Methods RNA-sequencing and bioinformatics analyses were performed to identify key mitochondrial ABC transporters and ABC transporter subfamily B member 7 (ABCB7)-mediated transcriptomic alterations. We investigated role of ABCB7 in iron homeostasis by examining iron concentration and reactive oxygen species (ROS) generation. Drug resistance and cellular survival mechanisms were understood by comparing the type and degree of cell death according to the ABCB7 expression. Results ABCB7 is highly expressed in patients with glioblastoma and has a negative correlation with prognosis. The increase in ABCB7 gives resistance to drug and the loss of ABCB7 leads to cell death. ABCB7 increases the expression of hypoxia-inducible factor 1 alpha (HIF1α) and activates HIF1α signaling by regulating iron concentration. When ABCB7 expression is maintained high in cancer cells, hypoxia-independent activation of HIF1α inhibits cell death by suppressing leucine zipper downregulated in cancer 1 (LDOC1). However, when ABCB7 is decreased, non-apoptotic cell death is induced by the change of iron concentration, and apoptosis which is inhibited by HIF1α signal is also induced. Additionally, because ABCB7 is essential for survival of universal cancer cells, it is presented as a pan-cancer core fitness gene. Conclusions Our findings demonstrate the ABCB7 inhibits both apoptotic and non-apoptotic cell death via maintenance of iron homeostasis and hypoxia-independent HIF1α signaling. Editorial acknowledgement Cancer Growth Regulation Laboratory for their discussion and technical assistance. Legal entity responsible for the study The authors. Funding National Research Foundation of Korea (NRF) [grant numbers: 2015R1A5A1009024 and 2017R1E1A1A01074205], the School of Life Sciences and Biotechnology for BK21 Plus, Korea University and Institute of Animal Molecular Biotechnology Korea University. Disclosure All authors have declared no conflicts of interest.

Effects of LDOC1 on colorectal cancer cells via downregulation of the Wnt/β-catenin signaling pathway.

Colorectal cancer (CRC) is one of the most common tumor types of the digestive tract. Its incidence and mortality rates are among the highest of all gastrointestinal tumor types. The expression of leucine zipper downregulated in cancer 1 (LDOC1) is decreased in numerous cancer types. In the present study, the aim was to investigate the role of LDOC1 and determine the potential molecular mechanisms of its action in CRC. The expression of LDOC1 in CRC tissues and adjacent normal tissues was detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. LDOC1 expression in four CRC cell lines, compared with normal colorectal tissue, was determined by reverse transcription- polymerase chain reaction (RT-PCR), and two cell lines with relatively low expression were screened. Human LDOC1 cDNA was inserted into a lentiviral vector, and transfected into HCT-116 and Caco2 cell lines. The transfection efficiency was identified by RT-PCR and western blot analysis. Cell proliferation was detected by Cell Counting Kit-8 and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry assay. Migration and invasion were assessed using Transwell and Matrigel assays, respectively. Additionally, whether LDOC1 regulates the Wnt/β-catenin pathway was investigated by western blot analysis, and the expression and localization of β-catenin in CRC cells were demonstrated by cellular immunofluorescence. LDOC1 expression was downregulated in CRC tissues and cells. LDOC1 overexpression inhibited cell proliferation, migration and invasion, but promoted cells apoptosis. Furthermore, LDOC1 downregulated the Wnt/β-catenin pathway in CRC. In conclusion, LDOC1 is a tumor suppressor in CRC and it inhibits cell proliferation and promotes cell apoptosis. Additionally, it inhibits CRC cell metastasis by downregulating the Wnt/β-catenin signaling pathway.

Novel STAT3 Inhibitor LDOC1 Targets Phospho-JAK2 for Degradation by Interacting with LNX1 and Regulates the Aggressiveness of Lung Cancer.

Meta-analysis revealed that Leucine Zipper Down-Regulated In Cancer 1 (LDOC1) increased methylation more in people with lung tumors than in those who were healthy and never smoked. Quantitative methylation-specific PCR revealed that cigarette smoke condensate (CSC) exposure drives LDOC1 promoter hypermethylation and silence in human bronchial cells. Immunohistochemistry studies showed that LDOC1 downregulation is associated with poor survival of patients with lung cancer. Loss and gain of LDOC1 functions enhanced and attenuated aggressive phenotypes in lung adenocarcinoma A549 and non–small cell lung carcinoma H1299 cell lines, respectively. We found that LDOC1 deficiency led to reinforcing a reciprocal loop of IL-6/JAK2/STAT3, through which LDOC1 mediates the cancer progression. LDOC1 knockdown considerably augmented tumorigenesis and the phosphorylation of JAK2 and STAT3 in vivo. Results from immunoprecipitation and immunofluorescent confocal microscopy indicated that LDOC1 negatively regulates JAK2 activity by forming multiple protein complexes with pJAK2 and E3 ubiquitin-protein ligase LNX1, and in turn, LDOC1 targets pJAK2 to cause ubiquitin-dependent proteasomal degradation. LDOC1 deficiency attenuates the interactions between LNX1 and pJAK2, leading to ineffective ubiquitination of pJAK2, which activates STAT3. Overall, our results elucidated a crucial role of LDOC1 in lung cancer and revealed how LDOC1 acts as a bridge between tobacco exposure and the IL-6/JAK2/STAT3 loop in this human malignancy.

LDOC1 (leucine zipper, down-regulated in cancer 1)

LDOC1 (leucine zipper, down-regulated in cancer 1)

NF-κB upregulation through epigenetic silencing of LDOC1 drives tumor biology and specific immunophenotype in Group A ependymoma.

Inflammation has been identified as a hallmark of high-risk Group A (GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors drives an immune suppressive phenotype by polarizing infiltrating monocytes. This study determines the mechanism by which IL-6 is dysregulated in GpA EPN. Twenty pediatric GpA and 21 pediatric Group B (GpB) EPN had gene set enrichment analysis for MSigDB Hallmark gene sets performed. Protein and RNA from patients and cell lines were used to validate transcriptomic findings. GpA cell lines 811 and 928 were used for in vitro experiments performed in this study. The nuclear factor-kappaB (NF-κB) pathway is a master regulator of IL-6 and a signaling pathway enriched in GpA compared with GpB EPN. Knockdown of NF-κB led to significant downregulation of IL-6 in 811 and 928. NF-κB activation was independent of tumor necrosis factor alpha (TNF-α) stimulation in both cell lines, suggesting that NF-κB hyperactivation is mediated through an alternative mechanism. Leucine zipper downregulated in cancer 1 (LDOC1) is a known transcriptional repressor of NF-κB. In many cancers, LDOC1 promoter is methylated, which inhibits gene transcription. We found decreased LDOC1 gene expression in GpA compared with GpB EPN, and in other pediatric brain tumors. EPN cells treated with 5AZA-DC, demethylated LDOC1 regulatory regions, upregulated LDOC1 expression, and concomitantly decreased IL-6 secretion. Stable knockdown of LDOC1 in EPN cell lines resulted in a significant increase in gene transcription of v-rel avian reticuloendotheliosis viral oncogene homolog A, which correlated to an increase in NF-κB target genes. These results suggest that epigenetic silencing of LDOC1 in GpA EPN regulates tumor biology and drives inflammatory immune phenotype.

LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients.

Osteosarcomas are common bone malignancies in children and adolescents. LDOC1 (leucine zipper, down-regulated in cancer 1), a tumor suppressor, is down-regulated in many cancers. In this study, we investigated the role of LDOC1 in tumor metastasis and its prognostic significance in osteosarcomas. We established osteosarcoma cells stably expressing LDOC1, driven by an HIV-based lentiviral system. We investigated the impact of LDOC1 on migration and invasion abilities in these cells using a transwell assay. LDOC1-associated changes in expression of metastasis-promoting genes were analyzed with a quantitative real-time polymerase chain reaction primer array. A xenograft tumor model (n = 7 mice/group) was used to assess the effect of LDOC1 on osteosarcoma metastasis in vivo. The overall survival and disease-free survival of osteosarcoma patients (n = 74) were analyzed retrospectively based on immunohistochemical analysis of LDOC1 levels in tumors and Kaplan-Meier analysis. LDOC1-expressing osteosarcoma cells displayed decreased migration and invasion in vitro. The quantitative real-time polymerase chain reaction primer array data showed that increased LDOC1 expression up-regulated many metastasis-suppressor genes. In the xenograft model, micro-computed tomography imaging data indicated that increased LDOC1 expression is associated with weaker lung metastasis ability. The Wnt5a signaling pathway promotes osteosarcoma metastasis; LDOC1 expression decreased Wnt5a levels in osteosarcoma cells. Kaplan-Meier analysis showed that higher LDOC1 expression was associated with improved osteosarcoma patient overall survival and disease free survival (p = 0.022). Our data show that LDOC1 is a tumor suppressor in osteosarcoma, and that it regulates metastasis of osteosarcoma cells. Furthermore, LDOC1 might be a valuable prognostic marker in osteosarcomas.

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer.

Numerous genetic alterations have been implicated in the development of prostate cancer (PCa). DNA and protein microarrays have enabled the identification of genes associated with apoptosis, which is important in PCa development. Despite the molecular mechanisms are not entirely understood, inhibition of apoptosis is a critical pathophysiological factor that contributes to the onset and progression of PCa. Leucine zipper, down-regulated in cancer 1 (LDOC-1) is a known regulator of the nuclear factor (NF)-mediated pathway of apoptosis through the inhibition of NF-κB. The present study investigated the expression of the LDOC-1 gene in LNCaP, PC-3, PNT1A and PNT2 prostate cell lines by reverse transcription-quantitative polymerase chain reaction. In addition LDOC-1 protein expression in normal prostate tissues and PCa was studied by immunohistochemistry. LDOC-1 messenger RNA resulted overexpressed in LNCaP and PC-3 PCa cell lines compared with the two normal prostate cell lines PNT1A and PNT2. The results of immunohistochemistry demonstrated a positive cytoplasmic LDOC-1 staining in all PCa and normal prostate samples, whereas no nuclear staining was observed in any sample. Furthermore, a more intense signal was evidenced in PCa samples. LDOC-1 gene overexpression in PCa suggests an activity of LDOC-1 in PCa cell lines.

LDOC1 gene expression in two patients with head and neck squamous cell carcinomas and Parkinson's disease.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Risk factors for this cancer include tobacco and alcohol use, ultraviolet light exposure, and viral infection. Parkinson's disease is one of the most common neurodegenerative disorders, with a prevalence of 3% in persons over the age of 65 years. Apoptosis is a programmed cell death machinery pivotal for normal development, the establishment of highly organized neuronal circuitry, and the elimination of cancer cells. It has been suggested that increased expression of proapoptotic genes is associated with head tumors. One of these genes is the leucine zipper, down-regulated in cancer 1 (LDOC1) gene. We report two interesting cases of a 79-year-old man and a 98-year-old woman, both with Parkinson's disease and well-differentiated multiple HNSCC, in whom we evaluated the possible differential expression of LDOC1. We found that LDOC1 gene expression was increased in both patients compared with three male and three female controls. Conclusions. These findings suggest that apoptosis may play a pathogenetic role in HNSCC.

LDOC1 expression in fibroblasts of patients with Down syndrome

Abstract Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms.

Epigenetic silencing of the LDOC1 tumor suppressor gene in ovarian cancer cells

Due to very unspecific symptoms ovarian cancer often is diagnosed only at a late stage of the disease. Thus, morbidity and mortality of the patients are high. Even the established tumor marker CA12-5 shows only low specificity, rising the need for alternative biomarkers capable of detecting early stages of ovarian cancer. We analyzed the expression of the tumor suppressor candidate gene LDOC1 (leucine zipper downregulated in cancer 1) as a potential early biomarker in ovarian cancer cell lines. A total of seven ovarian cancer cell lines were analyzed by RT-PCR (reverse transcriptase polymerase chain reaction) and real-time PCR for expression of LDOC1. Verification of promoter methylation was performed using methylation-specific primers on bisulfite-modified genomic DNA. Three out of seven ovarian cancer cell lines showed a complete loss of LDOC1 gene expression. LDOC1 silencing was caused neither by gene deletion nor gene rearrangements, but by methylation and subsequent inactivation of the concerned promoter as proofed by methylation specific primers. Similarly, promoter methylation could be inhibited by adding AdC (5-aza-2'-deoxycytidine), an inhibitor of DNA methyltransferases. As a result, a reactivation of the LDOC1 gene was seen. The tumor suppressor gene LDOC1 in ovarian cancer cell lines is downregulated by promoter methylation and thus may serve as an early biomarker. Further investigation will show if detection of methylated LDOC1 in peripheral blood has both adequate sensitivity and specificity for a timely non-invasive detection of ovarian cancer.

Overexpression of LDOC1 in Human Biliary Epithelial Cells Inhibits Apoptosis Through NF‐κB Signaling

Biliary atresia (BA) is a devastating pediatric cholestatic liver disease. Increasing evidence indicates that nuclear factor (NF)-κB signaling plays a key role in the pathogenesis of BA. Leucine zipper downregulated in cancer 1 (LDOC1) may control the expression of NF-κB. The aim of this study was to evaluate the relation between LDOC1 and inflammation/apoptosis mediated by NF-κB in the human intrahepatic biliary epithelial cells (HIBECs). HIBECs were divided into 3 treatment groups: control, mock transfection group, and LDOC1 transfection. Immunofluorescence, reverse transcription polymerase chain reaction, Western blot, and flow cytometry analysis were used to investigate the effectiveness of LDOC1-transfected HIBECs and the expression of NF-κB. Apoptosis was detected by Hochest/ propidium iodide staining. Interleukin (IL)-2 and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay. The expression of NF-κB was higher in the LDOC1-transfected group when compared with the control and mock-transfected groups as evaluated by immunofluorescence, reverese transcription polymerase chain reaction, and Western blot analysis. The rate of apoptosis was significantly lower in the LDOC1-transfected group when compared with the control and mock-transfected groups. The levels of IL-2 and TNF-α were significantly higher in the LDOC1-transfected group when compared with the control and mock-transfected groups. Upregulation of LDOC1 in HIBEC increases the expression of NF-κB, which may promote the activation of IL-2 and TNF-α secretion and inhibit cell apoptosis.

LDOC1 Gene Expression in Two Patients with Head and Neck Squamous Cell Carcinomas and Parkinson's Disease

Introduction Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world. Risk factors for this cancer include tobacco and alcohol use, ultraviolet light exposure, and viral infection. Parkinson's disease is one of the most common neurodegenerative disorders, with a prevalence of 3% in persons over the age of 65 years. Apoptosis is a programmed cell death machinery pivotal for normal development, the establishment of highly organized neuronal circuitry, and the elimination of cancer cells. It has been suggested that increased expression of proapoptotic genes is associated with head tumors. One of these genes is the leucine zipper, down-regulated in cancer 1 (LDOC1) gene. Case report We report two interesting cases of a 79-year-old man and a 98-year-old woman, both with Parkinson's disease and well-differentiated multiple HNSCC, in whom we evaluated the possible differential expression of LDOC1. Results We found that LDOC1 gene expression was increased in both patients compared with three male and three female controls. Conclusions These findings suggest that apoptosis may play a pathogenetic role in HNSCC.

Expression of LDOC1 mRNA in leucocytes of patients with Down’s syndrome

Down’s syndrome (DS), or trisomy 21, results from an extra chromosome 21 which is due to failure of normal chromosomal segregation during meiosis. Individuals with trisomy 21 can develop premature ageing and some traits of Alzheimer disease at an earlier age than subjects without trisomy 21 (Wisniewski et al. 1985). These individuals were thought to experience a neurodegenerative process because of the presence of an extra copy of the amyloid precursor protein (APP) gene located on chromosome 21, but this hypothesis has not been entirely confirmed by the literature (Elsayed and Elsayed 2009; Arriagada et al. 2010). Several studies have amply demonstrated that genes related to apoptosis play a crucial role in neurodegenerative diseases, indeed apoptotic pathways appear to play a causal role in neurodegenerative processes and in cancer proliferation (Engidawork and Lubec 2001; Gulesserian et al. 2001; Seidl et al. 2001; Yoo et al. 2001; Engidawork and Lubec 2001; Fromage and Anglade 2002; Lubec and Engidawork 2002). The cancer process is favoured when the apoptotic surveillance is, for any reason (Hu and Kavanagh 2003), decreased; conversely, when the apoptotic process is some what encouraged, neurodegenerative processes, such as those related to Alzheimer disease, will be prevailing (Elmore 2007). The leucine zipper, downregulated in cancer 1 (LDOC1) gene, was mapped on chromosome X at q27 and consists of only one exon (OMIM 300402). The Xq27 region is

Three apoptotic genes are upregulated in a patient with Alzheimer's disease and well-differentiated squamous cell carcinoma

We report the case of a 74-year-old man with Alzheimer's disease (AD) and an extensive ulcerative lesion on the right ear. AD is a neurodegenerative disease with progressive loss of memory and cognitive deterioration. It has been suggested that apoptotic cell injury and eventually cell death is a major contributor to the AD neurodegenerative process. The ulcerative lesion was surgically excised and the histological analysis reported a well-differentiated squamous cell carcinoma. Caspase-3 (CASP3) plays an important role in neuronal death during nervous system development and under certain pathological conditions. Furthermore, in vitro and in vivo studies reported elevated expression and activation of CASP3 in models of AD. Molecular epidemiological studies suggest that CASP3 may contribute to head and neck squamous cell carcinoma susceptibility and disease progression and that increased CASP3 expression is associated with tumors of the head. Also poly (ADP-ribose) polymerase 1 (PARP1) and the leucine zipper downregulated in cancer 1 (LDOC1) genes play a proapoptotic role. We therefore evaluated the differential expression of LDOC1, PARP1, and CASP3 mRNA in peripheral blood leukocytes of our patient. We found increased expression of all these genes compared with the expression in control subjects.