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Yan Geng

Publications and source records attributed to Yan Geng.

32 records · Page 2Linked to original sources
PubMed2005

Identification and classification of all potential hemolysin encoding genes and their products from Leptospira interrogans serogroup Icterohae-morrhagiae serovar Lai.

AIM: To identify and classify all potential hemolysin candidates of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai. METHODS: All of the potential hemolysin encoding genes were characterized in silico. These genes were cloned and expressed in Escherichia coli. The hemolytic activities of the expressed proteins were assayed observing the hemolysis on sheep blood agar plates. Sphingomyelinase activities of the hemolysin candidates were measured by thin-layer chromatography (TLC) and HPLC for sphingomyelin-hydrolysis. Expression and secretion of the hemolysins in L interrogans were studied by reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assays. RESULTS AND CONCLUSION: The hemolytic activities of hemolysin candidates (LA0327, LA0378, LA1027, LA1029, LA1650, LA3050, LA3937, LA4004) from L interrogans strain Lai were confirmed. They were further divided into two groups, sphingomyelinase hemolysins and non-sphingomyelinase hemolysins, based on their ability to hydrolyze sphingomyelin. Most of these hemolysins were actually expressed in living L interrogans and some of them were secreted into the environment. This study establishes an essential and complete basis for further studying the contribution of hemolysins to the pathogenesis of L interrogans.

Amino Acid Sequence↗
PubMed2005

Genetic replacement of cyclin D1 function in mouse development by cyclin D2.

D cyclins (D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. It is unclear whether each of the D cyclins performs unique, tissue-specific functions or the three proteins have virtually identical functions and differ mainly in their pattern of expression. We previously generated mice lacking cyclin D1, and we observed that these animals displayed hypoplastic retinas and underdeveloped mammary glands and a presented developmental neurological abnormality. We now asked whether the specific requirement for cyclin D1 in these tissues reflected a unique pattern of D cyclin expression or the presence of specialized functions for cyclin D1 in cyclin D1-dependent compartments. We generated a knock-in strain of mice expressing cyclin D2 in place of D1. Cyclin D2 was able to drive nearly normal development of retinas and mammary glands, and it partially replaced cyclin D1's function in neurological development. We conclude that the differences between these two D cyclins lie mostly in the tissue-specific pattern of their expression. However, we propose that subtle differences between the two D cyclins do exist and they may allow D cyclins to function in a highly optimized fashion. We reason that the acquisition of multiple D cyclins may allow mammalian cells to drive optimal proliferation of a diverse array of cell types.

Animals↗
PubMed2005

[Expression and significance of ADP-ribosylation factor 1 (ARF1) in colorectal laterally spreading tumor].

BACKGROUND & OBJECTIVE: Laterally spreading tumor (LST) behaves close to malignant tumor. This study was to search for the genes and functional proteins correlated to growth and development of colorectal LST (CLST), and to reveal the molecular mechanisms of CLST growth pattern and malignant transformation. METHODS: cDNA microarray was used to screen differentially expressed genes among CLST cell line and other 2 colorectal cell lines LoVo and SW480. Different mRNA and protein expressions of the genes were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Compared with LoVo and SW480 cells, 58 genes were up-regulated and 39 genes were down-regulated in CLST cells. mRNA level of ADP-ribosylation factor 1 (ARF1) was significantly higher in CLST cells than in SW480 and LoVo cells (0.93 vs. 0.74 and 0.47, P = 0.04); protein level of ARF1 was significantly higher in CLST cells than in LoVo cells. CONCLUSIONS: CLST has specific gene expression profile. ARF1 is overexpressed in CLST, and may mediate specific biological function of CLST.

ADP-Ribosylation Factor 1↗
PubMed2005

[Evaluation of IL-6 level in serum and bronchoalveolar lavage fluid of patients with non-small cell lung cancer (NSCLC)].

AIM: To study the relationship between the interleukin-6(IL-6) level in serum and broncheoalveolar lavage fluid(BALF) and non-small cell lung cancer(NSCLC). METHODS: The concentration of IL-6 in serum or BALF of 62 NSCLC patients, 36 patients of pulmonary inflammatory diseases (PID) and 25 normal controls were measured by ELISA. RESULTS: (1)The concentration of IL-6 in BALF of NSCLC patients was significantly higher than that of PID patients and normal controls (P<0.01). The concentration of IL-6 in sera of NSCLC patients was higher than that of normal controls (P<0.01) but not statistically different from that of PID patients. (2)In patients with NSCLC, the concentration of IL-6 in BALF was slightly higher than that of serum IL-6, but this difference was not statistically significant (P>0.05). (3)Serum IL-6 level was higher in NSCLC of advanced stages (stage IIIa, IIIb and IV), as compared with that in NSCLC patients of early stages (stage Ia-IIb). BALF IL-6 level of NSCLC patients at different stages was not different. (4)IL-6 (level in serum but not in BALF) of PID patients correlated with the serum concentration of C reactive protein (r=0.74). CONCLUSION: IL-6 in BALF might be used as a marker for NSCLC. Serum IL-6 level might be an indicator for the stage of NSCLC. The serum IL-6 can also reflect the severity of acute lung inflammatory response.

Acute-Phase Reaction↗
PubMed2004

Inhibition of NMU-induced mammary tumorigenesis by dietary soy.

We previously demonstrated that female Sprague-Dawley rats fed AIN-93G diets containing soy protein isolate (SPI+) had lower DMBA-induced mammary tumor incidence than those fed diets containing casein (CAS), due partly to altered Phase I metabolism with soy. Here, we evaluated the tumor protective effects of these same diets to the direct-acting carcinogen N-methyl-nitrosourea (NMU). Tumor incidence was reduced and tumor latency was enhanced, in NMU-administered female rats lifetime exposed to SPI+, relative to the CAS group. Tumor multiplicity did not differ with diet, while tumor grade tended to be more advanced with SPI+. Normal mammary glands of CAS and SPI+ tumor-bearing rats had comparable proliferative and apoptotic status. However, mammary expression of HER-2/neu and progesterone receptor (PR) genes was higher for SPI+ rats. Moreover, tumored SPI+ rats had lower serum progesterone levels than those fed CAS, while serum estrogen did not differ. Serum from tumored SPI+ rats had higher apoptotic activity towards mammary epithelial MCF-7 cells, than CAS serum. Thus, dietary soy protects against mammary tumorigenesis induced by a direct-acting carcinogen and alters signaling pathways involving PR and HER-2/neu.

Alkylating Agents↗
PubMed2004

Mouse development and cell proliferation in the absence of D-cyclins.

D-type cyclins (cyclins D1, D2, and D3) are regarded as essential links between cell environment and the core cell cycle machinery. We tested the requirement for D-cyclins in mouse development and in proliferation by generating mice lacking all D-cyclins. We found that these cyclin D1(-/-)D2(-/-)D3(-/-) mice develop until mid/late gestation and die due to heart abnormalities combined with a severe anemia. Our analyses revealed that the D-cyclins are critically required for the expansion of hematopoietic stem cells. In contrast, cyclin D-deficient fibroblasts proliferate nearly normally but show increased requirement for mitogenic stimulation in cell cycle re-entry. We found that the proliferation of cyclin D1(-/-)D2(-/-)D3(-/-) cells is resistant to the inhibition by p16(INK4a), but it critically depends on CDK2. Lastly, we found that cells lacking D-cyclins display reduced susceptibility to the oncogenic transformation. Our results reveal the presence of alternative mechanisms that allow cell cycle progression in a cyclin D-independent fashion.

Animals↗
PubMed2004

Dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis, and gene expression during postnatal development.

We have found that AIN-93G diets made with whey protein hydrolysate (WPH) reduce 7,12-dimethyl-benz[a]anthracene (DMBA)-induced tumor incidence in Sprague-Dawley (Harlan) rats relative to those fed a diet with casein (CAS). Herein, we replicated these findings in another Sprague-Dawley substrain (Charles River) and examined whether WPH protective effects were associated with altered mammary gland differentiation status and expression of the tumor suppressor phosphatase and tensin homolog deleted in chromosome ten (PTEN). Mammary tumor incidence was lower in DMBA-treated rats fed WPH than in those fed CAS. Mammary glands of WPH- and CAS-fed rats were isolated at weaning [postnatal day (PND) 21-28] and at an early adult stage (PND 50-53) and analyzed for proliferative (proliferating cell nuclear antigen immunoreactivity), apoptotic (terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labeling), and differentiation (beta-casein) indices, as well as for PTEN mRNA and protein levels. PND 50-53 rats fed WPH showed decreased proliferation and increased apoptosis in mammary structures, coincident with increased mammary beta-casein gene expression, decreased terminal end-bud numbers, and increased ductal lengths, relative to same-age CAS-fed rats. When challenged with DMBA for 24 h, mammary glands of PND 53 CAS-fed rats had decreased cell survival in both terminal end buds and ductal epithelium, while the mammary glands of WPH-fed rats were not altered from pre-DMBA levels. At 7 d post-DMBA, mammary glands of CAS- and WPH-fed rats exhibited comparable apoptotic indices. Mammary PTEN expression was higher in WPH- than in CAS-fed rats at PND 21-28, but was not different in young adults fed either diet. Results demonstrate that dietary WPH advances mammary gland differentiation during neonatal development and suggest that the transiently increased expression of the pro-apoptotic signal PTEN during a sensitive developmental window may partly underlie the cancer protective effects of WPH.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

[Screening of differentially expressed genes related to laterally spreading tumor by cDNA microarray].

OBJECTIVE: To screen differentially expressed genes between laterally spreading tumor (LST) cell line and common colon carcinoma cell lines, and identify new targets and strategies for exploring the pathogenesis of colorectal tumor. METHODS: The total RNA was extracted from the LST, SW480 and LoVo cells, from which purified mRNAs were obtained. The PCR products of 18 816 genes were blotted onto a fibrous membrane to generate the microarray. The mRNAs from the 3 cell lines were reversely transcribed into cDNA probes and labeled with (33)P before hybridization with the cDNA microarray. After thorough washing, the cDNA microarray was scanned and the 3 samples compared. RESULTS AND CONCLUSIONS: A series of differentially expressed genes were found between the 3 samples, and 58 up-regulated and 39 down-regulated genes were identified among the 97 differentially expressed genes, which suggest different pathogeneses of the laterally spreading tumor. Further analysis of the obtained genes can be helpful in understanding the molecular mechanism of colorectal tumors.

Cell Line, Tumor↗
PubMed2003

Cyclin E ablation in the mouse.

E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent G(0) state. Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation.

Animals↗
PubMed2003

Requirement for cyclin D3 in lymphocyte development and T cell leukemias.

The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3(-/-) animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies.

Animals↗
PubMed2002

Cellular and molecular targets of estrogen in normal human breast tissue.

To gain insight into the in vivo role of estrogen, we isolated estrogen receptor-positive cells fromnormal human breast tissue using a recombinant adenovirus that expresses green fluorescence protein in response to estrogen. We compared the global gene expression profile of these estrogen receptor-positive cells with that of various normal and cancerous mammary epithelial cells and identified several genes not implicated previously in estrogen signaling. One of these genes, lipocalin 2, is a putative in vivo estrogen target gene and paracrine factor that mediates the growth regulatory effects of estrogen in normal breast epithelium. These results demonstrate that normal and cancerous estrogen receptor-positive cells are distinct at the molecular level and suggest that lipocalin 2 is a new therapeutic target for breast cancer prevention and treatment.

Adenoviridae↗