Disease relevance of PLEKHB1

• The effect of synthetic DADS on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MDA-MB-231 and MKL-F) human breast cancer cell lines was examined [1].
• Metastasis was seen in the JYG-A, JYG-B, and KPL-1 cells [2].
• In an in vivo assay using JYG-A, JYG-B, KPL-1, and MDA-MB-231 cells by orthotopic (right thoracic mammary fat pad) transplantation in female nude mice, TNP-470 at 30 or 50 mg/kg body weight was injected s.c. every other day from the day of tumor cell inoculation until the end of the experiment [2].
• In in vitro experiments, extracts of this alga inhibited not only the growth of several tumor cell lines, such as B16-BL6 (a mouse melanoma cell line), JYG-B (a mouse mammary carcinoma cell line) and KPL-1 (a human mammary carcinoma cell line), but also invasion of B16-BL6 cells in a culture system [3].
• This MAb, an IgG1kappa, designated PHR1, recognizes human GARFT by both Western blot and by immunohistochemistry from non-small-cell lung carcinoma and colon adenocarcinoma tissue biopsies, has a KD of 1.14 x 10(10) M, and has been epitope mapped at residues 59-78 of the GARFT functional domain [4].

High impact information on PLEKHB1

• We have isolated a DNA photolyase gene (phr1) from Trichoderma harzianum, a common soil fungus that is of interest as a biocontrol agent against soil-borne plant pathogens and as a model for the study of light-dependent development [5].
• Further analysis showed that on E-selectin, KPL1 blocked only secondary (i.e., monocyte/monocyte) interactions, but did not block primary (i.e., monocyte/E-selectin) interactions, with secondary adhesion accounting for 90% of the total adhesive interactions on either E- or P-selectin [6].
• Both mRNA expression and secretion of VEGF were stimulated by MPA in KPL-1 cells, but in E2-dependent ML-20 cells they were both inhibited by MPA [7].
• E2 stimulated the growth of KPL-1 cells but MPA inhibited it in vitro [7].
• In contrast, E2 propionate inhibited the growth of KPL-1 cells in female nude mice but Ovex and MPA stimulated it [7].

Chemical compound and disease context of PLEKHB1

• In our previous study, the growth of KPL-1 human breast cancer cells was found to be stimulated by an antiestrogen, ICI 182, 780, and inhibited by 17 beta-estradiol (E2) in vivo but not in vitro [7].
• A pure antiestrogen, ICI 182,780, stimulates the growth of tamoxifen-resistant KPL-1 human breast cancer cells in vivo but not in vitro [8].
• The effect of synthetic resveratrol on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MKL-F) human breast cancer cell lines was examined [9].
• The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP-470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA-MB-231, T-47D, MCF-7, KPL-1, and MKL-F) [10].
• Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action [11].

Biological context of PLEKHB1

• As a new member of the family of PH domain-containing proteins, KPL1 may have a unique role in ciliated cell differentiation or function [12].
• The KPL1 protein is predicted to contain a pleckstrin homology (PH) domain, which has been found in numerous signal transduction and cytoskeletal proteins [12].
• These data suggest that this KPL-1 cell line may be useful for studying oestrogen-independent growth and the kinetics of tumour-associated antigens in vivo as well as in vitro [13].
• E2 propionate suppressed angiogenesis and increased apoptosis in KPL-1 tumors, but Ovex and MPA promoted angiogenesis and decreased apoptosis [7].
• RNaseLX promoter sequences contained the conserved binding motif of the transcription factor PHR1 known to mediate phosphate starvation-dependent gene expression [14].

Anatomical context of PLEKHB1

• KPL1, which encodes a novel PH domain-containing protein, is induced during ciliated cell differentiation of rat tracheal epithelial cells [12].
• Paracrine interaction between tumor cells and stromal cells mediated by growth factors, such as FGF-1, might be a key factor to explain the unique hormone responsiveness of KPL-1 cells [8].
• POH at a dose of 75 mg/kg administered intraperitoneally three times a week throughout the entire 6-week experimental period suppressed orthotopically transplanted KPL-1 tumor cell growth and regional lymph node metastasis in a nude mouse system [15].
• By Northern blot analyses we found RZR alpha mRNA expressed in a variety of organs, whereas a high amount of PHR-1 mRNA was found in pancreas and less in liver [16].
• It better inhibits P-selectin-PSGL-1 interactions than a commercially available murine monoclonal antibody KPL1 and better inhibits neutrophil rolling than KPL1 [17].

Associations of PLEKHB1 with chemical compounds

• KPL1, an adhesion-blocking mAb directed against the tyrosine sulfate motif of PSGL-1, abolished monocyte-adhesive interactions with P-selectin, but only partially blocked monocyte interaction with E-selectin [6].
• TNP-470 significantly inhibited the growth of KPL-1 tumors stimulated by MPA [7].
• Resveratrol at low concentrations caused cell proliferation in ER-positive lines (KPL-1, < or = 22 microM; MCF-7, < or = 4 microM) whereas at high concentrations (> or = 44 microM) it caused suppression of cell growth in all three cell lines examined [9].
• Many cell lines such as BT 20, KPL-1, and T47D expressed abundant MUC1 whilst others such as MDA-MB-231 and MCF-7 showed intermediate expression, and MDA-MB-435 and MDA-MB-453 expressed very low levels [18].
• The ability of PHR1 to recognize both sodium dodecyl sulfate (SDS)-denatured as well as native GARFT should make this MAb an important research tool in determining GARFT protein levels in both normal and neoplastic tissues [4].

Other interactions of PLEKHB1

• KPL1 was upregulated in RTE cultures undergoing mucociliary but not squamous differentiation; and in cultures undergoing mucociliary differentiation, KPL1 expression most closely paralleled that of a marker of ciliated cell differentiation (axonemal dynein heavy chain) and not a marker of mucous cell differentiation (mucin 5AC) [12].
• FGF-1 was overexpressed only in KPL-1 cells [8].
• These findings suggest that the abnormal modulation of VEGF expression by MPA and of the other angiogenic factor by E2 are responsible for the paradoxical growth responses of KPL-1 cells in vivo [7].
• The expression vector of ER alpha C/D was transfected to the human cancer cell, KPL-1, which expressed the intrinsic ER [19].
• PHR-1 turned out to be the human homologue of the recently published murine LRH-1 [16].

Analytical, diagnostic and therapeutic context of PLEKHB1

• In the 50 mg/kg TNP-470-treated group, the reductions in tumor weight of the JYG-A, JYG-B, KPL-1, and MDA-MB-231 cells with respect to the controls were 50%, 30%, 4%, and 49%, respectively [2].

References