Project description:PLAC1, cancer-testis antigen, is a crucial element in tumorigenesis and development programs for many cancers. Overexpression of PLAC1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo. Co-immunoprecipitation and immunofluorescence cell staining assays be used revealed that PLAC1 physically interact with Furin to degrade Notch1 and generate NICD (Notch1 intracellar domain) and further inhibit Pten, which is also supported by the microarray analysis.
Project description:Plac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1).
Project description:Plac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1). The RNeasy Mini Kit was used to purify total RNA from three independent cell culture samples for gene expression analysis. After isolation in parallel, 1 μg of each of the total RNA from E0771/Scram or E0771/Shplac1 was pooled prior to microarray gene expression analysis. E0771/Scram was considered as control group in this experiment.
Project description:Placenta enriched 1 (PLAC1) is a highly conserved X chromosome-linked gene prominently expressed in the mammalian placenta. The functions of PLAC1 in placentation have yet to emerge fully. The rat shares hemochorial placentation and deep intrauterine trophoblast cell invasion with the human. Herein, we investigated the expression and biological activities of PLAC1 in the rat and human placenta. Plac1 transcripts were prominently expressed in the junctional zone of the rat placenta, a structure analogous to the extravillous trophoblast cell column of the human placentation site, and in invasive trophoblast cells. A PLAC1 mutant rat model was generated using CRISPR/Cas9 genome editing and used to investigate the role of PLAC1 in rat placentation. Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, and a prominent depletion of invasive trophoblast cells within the uterine parenchyma. PLAC1 was required for rat trophoblast stem (TS) cell differentiation. In human TS cell development, PLAC1 does not contribute to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead, PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.
Project description:Placenta enriched 1 (PLAC1) is a highly conserved X chromosome-linked gene prominently expressed in the mammalian placenta. The functions of PLAC1 in placentation have yet to emerge fully. The rat shares hemochorial placentation and deep intrauterine trophoblast cell invasion with the human. Herein, we investigated the expression and biological activities of PLAC1 in the rat and human placenta. Plac1 transcripts were prominently expressed in the junctional zone of the rat placenta, a structure analogous to the extravillous trophoblast cell column of the human placentation site, and in invasive trophoblast cells. A PLAC1 mutant rat model was generated using CRISPR/Cas9 genome editing and used to investigate the role of PLAC1 in rat placentation. Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, and a prominent depletion of invasive trophoblast cells within the uterine parenchyma. PLAC1 was required for rat trophoblast stem (TS) cell differentiation. In human TS cell development, PLAC1 does not contribute to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead, PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.
Project description:Placenta enriched 1 (PLAC1) is a highly conserved X chromosome-linked gene prominently expressed in the mammalian placenta. The functions of PLAC1 in placentation have yet to emerge fully. The rat shares hemochorial placentation and deep intrauterine trophoblast cell invasion with the human. Herein, we investigated the expression and biological activities of PLAC1 in the rat and human placenta. Plac1 transcripts were prominently expressed in the junctional zone of the rat placenta, a structure analogous to the extravillous trophoblast cell column of the human placentation site, and in invasive trophoblast cells. A PLAC1 mutant rat model was generated using CRISPR/Cas9 genome editing and used to investigate the role of PLAC1 in rat placentation. Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, and a prominent depletion of invasive trophoblast cells within the uterine parenchyma. PLAC1 was required for rat trophoblast stem (TS) cell differentiation. In human TS cell development, PLAC1 does not contribute to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead, PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.
Project description:Placenta enriched 1 (PLAC1) is a highly conserved X chromosome-linked gene prominently expressed in the mammalian placenta. The functions of PLAC1 in placentation have yet to emerge fully. The rat shares hemochorial placentation and deep intrauterine trophoblast cell invasion with the human. Herein, we investigated the expression and biological activities of PLAC1 in the rat and human placenta. Plac1 transcripts were prominently expressed in the junctional zone of the rat placenta, a structure analogous to the extravillous trophoblast cell column of the human placentation site, and in invasive trophoblast cells. A PLAC1 mutant rat model was generated using CRISPR/Cas9 genome editing and used to investigate the role of PLAC1 in rat placentation. Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, and a prominent depletion of invasive trophoblast cells within the uterine parenchyma. PLAC1 was required for rat trophoblast stem (TS) cell differentiation. In human TS cell development, PLAC1 does not contribute to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead, PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.
Project description:A testis specific antigen, TSA70 was identified in the lab which was homolgous to the sperm tail outer dense fiber protein (ODF2). ODFs are disulphide stabilised during epididymal maturation and are required for sperm motility. ODF2 is reported to bind macrophage migration inhibitory factor (MIF), a moonlighting oxidoreductase. It is not known whether such proteins exist in the female reproductive tract that ensure the disulphide stability. The aim was to identify full quorum of such redundant proteins in both male and female reproductive tract fluids. Using recombinant testis specific antigen, TSA70/ODF2, as bait we report the identification of binding partners from the epididymal fluid. Since MIF is a 12.5kDa protein, we focussed only on the low molecular weight proteins.