Disease relevance of NDC80

• Addition of cGMP to cytosol of human endometrium or to cells of the endometrial cancer line HEC-1 produced severalfold increases in specific estrogen binding (EB) levels [1].
• Functional activity of purified IgG was assessed for the ability to block transcytosis of cell-associated HIV-1 through a tight monolayer of endometrial epithelial cell line HEC1 [2].
• Resistance to interferon of a human adenocarcinoma cell line, HEC-1, and its sensitivity to natural killer cell action [3].
• Correlation between susceptibility to the anticellular effect of human interferon (HuIFN) and ultraviolet (uv) lethality was examined in a set of isogeneous human cell lines (RSa and IFr cells), a human endometrial cancer cell line (HEC-1 cells), and a Xeroderma pigmentosum-derived fibroblast cell line ( CRL1200 cells) [4].
• Similar cyclic nucleotide dependent effects have now been demonstrated in homogenates prepared from a second endometrial cell line, HEC 50, and from two breast cancer cell lines, CG-5 and T47D [5].

High impact information on NDC80

• We report here that Ndc80/Hec1 functions in regulating kinetochore microtubule plus-end dynamics and attachment stability [6].
• The N terminus of Hec1 is phosphorylated by Aurora B kinase in vitro, and cells expressing N-terminal nonphosphorylatable mutants of Hec1 exhibit an increase in merotelic attachments, hyperstretching of centromeres, and errors in chromosome segregation [6].
• One of the gene products, Ndc80p, shows homology to human HEC protein (Chen, Y., D.J. Riley, P-L. Chen, and W-H. Lee. 1997. Mol. Cell Biol. 17:6049-6056) and temperature-sensitive mutants show defects in chromosome segregation [7].
• Addition of sodium molybdate, ATP, and GTP to homogenates of endometrial tissue or HEC-1 cells produces increases in EB levels similar to those obtained by the addition of cGMP [1].
• The products of this HEC-1 oligoisoadenylate synthetase consist mainly of dimers, trimers, and tetramers as found in other cell lines after interferon treatment [8].

Chemical compound and disease context of NDC80

• We have made progressive NH2-terminal and other segment deletions and ligations in the A/B domain, and studied the transcriptional activity of these mutant ERs in ER-negative MDA-MB-231 human breast cancer and HEC-1 human endometrial cancer cells [9].
• CONCLUSION: These results indicate that somatostatin analog RC-160 inhibits the growth of HEC-1 human endometrial cancer cells, thus implying its potential clinical utility in treating endometrial cancer [10].
• Metabolism and effects of progesterone in the human endometrial adenocarcinoma cell line HEC-1 [11].
• N. gonorrhoeae was inoculated onto polarized human endometrial carcinoma cell (HEC 1-B) monolayers, and at various intervals monolayers were washed and incubated with media containing gentamicin or media alone [12].
• The growth inhibitory effects of medroxyprogesterone acetate (MPA) and tamoxifen (TAM) were tested on three long-established endometrial carcinoma cell lines (HEC-1, KLE, and RL95-2) and on UM-EC-1, a new endometrial carcinoma cell line established in our laboratory [13].

Biological context of NDC80

• Architecture of the human ndc80-hec1 complex, a critical constituent of the outer kinetochore [14].
• These results suggest that the HEC protein may play an important role in chromosome segregation during M phase [15].
• HEC protein is expressed most abundantly in the S and M phases of rapidly dividing cells but not in terminal differentiated cells [15].
• HEC, a novel nuclear protein rich in leucine heptad repeats specifically involved in mitosis [15].
• Inactivation of HEC by microinjection of specific monoclonal antibodies into cells during interphase severely disturbs the subsequent mitoses [15].

Anatomical context of NDC80

• Hec1 and nuf2 are core components of the kinetochore outer plate essential for organizing microtubule attachment sites [16].
• Here, we show that depletion of either Nuf2 or Hec1 by RNAi in HeLa cells results in reduction of both proteins at kinetochores and in the cytoplasm [17].
• The ERbetacx transcript is expressed in testis, ovary, thymus and prostate as well as in human cultured cell lines such as HEC-1, HOS-TE85 and Saos-2 cells [18].
• Moreover, a polyclonal antibody, anti HEC1, specifically immunoprecipitated the BRL 3A BP from the same conditioned media, as well as from rat cerebrospinal and amniotic fluid and from conditioned medium of cells isolated from the neurointermediate lobe of adult rat pituitary [19].
• However, HEC-1 cells were susceptible to the cytotoxicity of natural killer (NK) cells, and interferon enhanced such NK activity [3].

Associations of NDC80 with chemical compounds

• The protein encoded by the human gene HEC (highly expressed in cancer) contains 642 amino acids and a long series of leucine heptad repeats at its C-terminal region [15].
• Here we show that human Hec1 is a serine phosphoprotein and that it binds specifically to the mitotic regulatory kinase Nek2 during G(2)/M [20].
• Estradiol increased steady-state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1-A cells [21].
• Epidermal growth factor-stimulated proliferation of HEC-1 cells was inhibited by RC-160 in a dose-dependent manner [10].
• The growth of HEC cells was unaffected by either progesterone or medroxyprogesterone acetate, a slowly metabolized progestin, at about 10(-6) M levels but was inhibited by about 10(-5) M concentrations of these compounds [11].

Regulatory relationships of NDC80

• In addition, HEC inhibits the proteolysis of mitotic cyclin B in vitro [22].

Other interactions of NDC80

• Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2 [23].
• Here we show that ablation of proteins required for MT-kinetochore attachment (Hec1/Ndc80, Nuf2 ) disrupts RanGAP1 and RanBP2 targeting to kinetochores [24].
• RNA interference-mediated depletion of hSPC25 in HeLa cells caused aberrant mitosis, followed by cell death, a phenotype similar to that of cells depleted of HEC1 [25].
• Matrix metalloproteinase (MMP)-2 and -9 are secreted and translocated from endometrial stromal cells to HEC-1 A cells in a steroid-dependent manner [26].
• The levels of IL-8 mRNA in SPEC-2 cells established from stage IV serous papillary adenocarcinoma were three-fold higher as compared to endometrial adenocarcinoma cells, HEC-1 A, established from stage IA endometrial cancer [27].

Analytical, diagnostic and therapeutic context of NDC80

• Fluorescence light microscopy, live cell imaging, and electron microscopy provide quantitative data demonstrating that Nuf2 and Hec1 are essential for normal kinetochore microtubule attachment [16].
• Further investigation revealed that testes organ culture, similarly, inhibited HEC-1 cell growth [28].
• Deglycosylation with endoglycosidase F, and immunoprecipitation with alpha HEC1 antibody revealed these proteins to be hIGFBP-3 and hIGFBP-2, respectively [29].
• Using surface biotinylation and immunofluorescence, the polyimmunoglobulin receptor was found to be expressed on the basolateral surface of HEC-1 monolayers [30].
• The 3D coculture of endometrial stromal and cancer cell lines (HEC-1 A, HEC-IB, or KLE) were maintained in the presence or absence of HGF [26].

References