The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers

Breast cancer is a major chronic disease threatening women's health. It has topped the global cancers as the diagnosed cases outnumbered lung cancer patients in 2020. Internal damage due to the seven emotions is an important cause of breast cancer and the disorders of hypothalamic-pituitary-adrenal(HPA) axis and endocrine system and the abnormal immune defense mechanism in response to psychological stress all affect the occurrence and development of breast cancer. It is noteworthy that the theory of seven emotions in traditional Chinese medicine and the psychological stress theory of modern medicine have something in common in some aspects. Therefore, this study explored the correlation between internal damage due to the seven emotions and psychological stress and analyzed the molecular biological mechanisms of psychological stress influencing breast cancer from the perspective of modern medicine, which is helpful to reasonably prevent breast cancer and other related tumors and improve the prognosis of breast cancer patients through emotion regulation.
Breast Neoplasms/genetics* ; Emotions ; Female ; Humans ; Hypothalamo-Hypophyseal System ; Medicine, Chinese Traditional ; Pituitary-Adrenal System ; Stress, Psychological

DNA methylation is closely related to the genesis and development of pituitary adenoma. Studies have shown that high methylation in the promoter region of potassium voltage-gated chanel,shaker related subfamily,beta member 2,O-6-methylguanine-DNA methyltransferase,echinoderm microtubule associated protein like 2 ,ras homolog family member D ,homeobox B1 ,NNAT, and P16 inhibits the expression of these genes and regulates of the proliferation of pituitary adenoma. DNA methylation is also closely related to invasive pituitary adenoma. Therefore,further study on molecular mechanism of DNA methylation of pituitary adenoma will offer a new strategy for the diagnosis and treatment of pituitary adenoma.
Adenoma ; genetics ; DNA Methylation ; Gene Expression Regulation, Neoplastic ; Humans ; Pituitary Neoplasms ; genetics ; Promoter Regions, Genetic

Pituitary adenomas (PAs) are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. ErbB receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor (EGFR) can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1 ( LRIG1), a negative mediated gene of ErbB receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.
Animals ; Apoptosis ; genetics ; Brain Neoplasms ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; genetics ; Membrane Glycoproteins ; biosynthesis ; genetics ; Mice ; Oncogene Protein v-akt ; biosynthesis ; Phosphatidylinositol 3-Kinases ; genetics ; Pituitary Neoplasms ; genetics ; pathology ; Xenograft Model Antitumor Assays ; raf Kinases ; biosynthesis ; genetics

OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Alphapapillomavirus/genetics ; *Atypical Squamous Cells of the Cervix/pathology/virology ; Cell Adhesion Molecules/genetics ; *DNA Methylation ; Female ; Genotype ; Humans ; Immunoglobulins/genetics ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics ; Paired Box Transcription Factors/genetics ; Papanicolaou Test ; Pituitary Adenylate Cyclase-Activating Polypeptide/genetics ; ROC Curve ; Squamous Intraepithelial Lesions of the Cervix/*genetics/pathology/virology ; Uterine Cervical Neoplasms/*genetics/pathology/virology ; Vaginal Smears

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant disease, characterized by low penetrance, early-onset disease, more invasive tumor growth, as well as somatotroph and lactotroph adenomas in most cases. It has been indicated that the aryl hydrocarbon receptor interacting protein (AIP) gene is a tumor suppressor gene. Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. However, the exact molecular mechanism by which its disfunction promotes tumorigenesis of pituitary is unclear.
Growth Hormone-Secreting Pituitary Adenoma ; genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Pituitary Neoplasms ; genetics

OBJECTIVE: To explore whether oncogenes DJ-1 and HSP27 are associated with invasiveness of human pituitary adenoma. METHODS: Total proteins were extracted from samples of 20 invasive and 20 non-invasive pituitary adenomas and the expression of DJ-1 and HSP27 was analyzed by Western blot. The correlation of DJ-1and HSP27 with the invasiveness of pituitary adenoma was analyzed. RESULTS: The strong positive rates of DJ-1 and HSP27 in the 20 invasive pituitary adenoma were 70% (14/20) and 80% (16/20), respectively. The invasive group had significantly higher expression of DJ-1 and HSP27 proteins than the noninvasive group [10% (2/20), 10% (2/20), respectively]. There was a positive correlation between the expression of DJ-1, HSP27 proteins and the invasiveness of pituitary adenoma as judged by the Spearman rank correlation test (P<0.05). CONCLUSION The proliferative activity and abnormal expression of oncogenes DJ-1 and HSP27 may play a significant role in tumorigenesis and progression of pituitary adenoma. There was a significant correlation between the expression of DJ-1 and HSP27 and the invasiveness of pituitary adenoma.
Adenoma ; metabolism ; pathology ; Adult ; Biomarkers, Tumor ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; HSP27 Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Middle Aged ; Neoplasm Invasiveness ; Oncogene Proteins ; genetics ; metabolism ; Pituitary Neoplasms ; metabolism ; pathology ; Protein Deglycase DJ-1 ; Signal Transduction ; Young Adult

OBJECTIVEWe examined alterations in the expression of tumorigenesis-related genes in the pituitary gland of rats exposed to electromagnetic pulses (EMP).

METHODSThe global gene expression profiles of the pituitary gland in EMP-exposed and control groups were detected by cDNA microarray analysis. We then validated and further investigated the reduced expression of two tumorigenesis-related genes, Pten, and Jund, by assessing their mRNA and protein expression by quantitative real-time-PCR, western blotting, and immunohistochemistry in the pituitary gland of rats 6 months after exposure to EMP.

RESULTSEMP exposure induced genome-wide gene expression changes in the rat pituitary gland. There was decreased expression of the Pten and Jund mRNAs and proteins in EMP-exposed rats compared with in unexposed control animals.

CONCLUSIONEMP exposure alters the expression of tumorigenesis-related genes in the pituitary gland. These tumorigenesis-related genes are potentially involved in the development of pituitary gland tumors in rats.

Adenoma ; genetics ; metabolism ; pathology ; Animals ; Down-Regulation ; Electromagnetic Phenomena ; Female ; Gene Expression Profiling ; Oligonucleotide Array Sequence Analysis ; PTEN Phosphohydrolase ; genetics ; metabolism ; Pituitary Gland ; metabolism ; Pituitary Neoplasms ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins c-jun ; genetics ; metabolism ; Rats ; Rats, Wistar ; Real-Time Polymerase Chain Reaction

BACKGROUNDControl of hypersecretion of certain hormones is one of the key targets in the treatment of pituitary adenomas. RNA interference has been shown to inhibit protein expression, and thus it may represent a promising method for the treatment of pituitary adenomas. In the present study, transfection efficiency of small interfering RNA (siRNA) was optimized in human prolactinoma cells.

METHODSFirst, a method was optimized to extract highly purified human prolactinoma cells in vitro. The extracted cells were verified to retain the physiological features of prolactin (PRL) secretion. Second, three conditions for siRNA transfection were tested by the evaluation of transfection efficiency and cell viability. The proper transfection condition was verified for human prolactinoma cells. Third, the siRNA for prolactin was transfected into the human prolactinoma cells, and the suppression of PRL mRNA was evaluated by quantitative real-time reverse transcription-PCR.

RESULTSThe siRNA of 100 pmol with Lipofectamine 2000 of 5 µl for 1 × 10(6) cells was proved preferable, with transfection efficiency being 53.3% and cell viability being 69.7%. In the preliminary experiment the siRNA against PRL decreased the mRNA of PRL by 34.0%.

CONCLUSIONIt is possible to inhibit hormone hypersecretion by RNA interference, that may eventually enable therapeutic siRNA drugs developed.

Adolescent ; Adult ; Cell Line, Tumor ; Cell Separation ; Female ; Humans ; Male ; Middle Aged ; Pituitary Neoplasms ; pathology ; therapy ; Prolactinoma ; pathology ; therapy ; RNA, Small Interfering ; genetics ; Transfection

Along with the rapid development of molecular biology, cell biology, genetics, and immunology, there is a new understanding on the pathogenesis of pituitary adenomas. The pathogenesis of pituitary adenomas is considered to be related with gene mutation, growth factors, cell receptors, transcription factors, and cellular signaling pathways.
Adenoma ; genetics ; metabolism ; Humans ; Mutation ; Pituitary Neoplasms ; genetics ; metabolism ; Signal Transduction