Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolactin (PRL) receptors (PRLRs) have been considered selective activators of Janus tyrosine kinase (Jak)2 but not Jak1, Jak3, or Tyk2. We now report marked PRL-induced tyrosine phosphorylation of Jak1, in addition to Jak2, in a series of human breast cancer cell lines, including T47D, MCF7, and SKBR3. In contrast, PRL did not activate Jak1 in immortalized, noncancerous breast epithelial lines HC11, MCF10A, ME16C, and HBL-100, or in CWR22Rv1 prostate cancer cells or MDA-MB-231 breast cancer cells. However, introduction of exogenous PRLR into MCF10A, ME16C, or MDA-MB-231 cells reconstituted both PRL-Jak1 and PRL-Jak2 signals. In vitro kinase assays verified that PRL stimulated enzymatic activity of Jak1 in T47D cells, and PRL activated Jak1 and Jak2 with indistinguishable time and dose kinetics. Relative Jak2 deficiency did not cause PRLR activation of Jak1, because overexpression of Jak2 did not interfere with PRL activation of Jak1. Instead, PRL activated Jak1 through a Jak2-dependent mechanism, based on disruption of PRL activation of Jak1 after Jak2 suppression by 1) lentiviral delivery of Jak2 short hairpin RNA, 2) adenoviral delivery of dominant-negative Jak2, and 3) AG490 pharmacological inhibition. Finally, suppression of Jak1 by lentiviral delivery of Jak1 short hairpin RNA blocked PRL activation of ERK and signal transducer and activator of transcription (Stat)3 and suppressed PRL activation of Jak2, Stat5a, Stat5b, and Akt, as well as tyrosine phosphorylation of PRLR. The data suggest that PRL activation of Jak1 represents a novel, Jak2-dependent mechanism that may serve as a regulatory switch leading to PRL activation of ERK and Stat3 pathways, while also serving to enhance PRL-induced Stat5a/b and Akt signaling.
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PMID:Coactivation of janus tyrosine kinase (Jak)1 positively modulates prolactin-Jak2 signaling in breast cancer: recruitment of ERK and signal transducer and activator of transcription (Stat)3 and enhancement of Akt and Stat5a/b pathways. 1755 Sep 76

A new series of 3-allylthio-6-(mono or disubstituted) aminopyridazines was synthesized by reacting 3-allylthio-6-chloropyridazine with several amines to develop new anticancer agents. These new compounds showed antiproliferative activities against lung cancer (A549), hepatoblastoma (Hep3b), prostate cancer (PC3), colon cancer (SW480) and cervical cancer (HeLa) cells in MTT assays, and could be promising candidates for chemotherapy of carcinomas. Compound 5 (3-allylthio-6-homopiperidinylaminopyridazine) showed higher potencies than 5-FU for inhibiting the growth of these cell lines. This suggests the potential anticancer activity of compound 5.
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PMID:Synthesis and anticancer activities of new 3-allylthio-6-(mono or disubstituted)aminopyridazines. 2019 17

Ribosomopathies comprise a heterogeneous group of hematologic and developmental disorders, often characterized by bone marrow failure, skeletal and other developmental abnormalities and cancer predisposition. They are associated with mutations and/or haplo-insufficiencies of ribosomal proteins (RPs) and inefficient ribosomal RNA (rRNA) processing. The resulting ribosomal stress induces the canonical p19ARF/Mdm2/p53 tumor suppressor pathway leading to proliferative arrest and/or apoptosis. It has been proposed that this pathway is then inactivated during subsequent neoplastic evolution. We show here that two murine models of hepatoblastoma (HB) and hepatocellular carcinoma (HCC) unexpectedly possess features that mimic the ribosomopathies. These include loss of the normal stoichiometry of RP transcripts and proteins and the accumulation of unprocessed rRNA precursors. Silencing of p19ARF, cytoplasmic sequestration of p53, binding to and inactivation of Mdm2 by free RPs, and up-regulation of the pro-survival protein Bcl-2 may further cooperate to drive tumor growth and survival. Consistent with this notion, re-instatement of constitutive p19ARF expression in the HB model completely suppressed tumorigenesis. In >2000 cases of human HCC, colorectal, breast, and prostate cancer, RP transcript deregulation was a frequent finding. In HCC and breast cancer, the severity of this dysregulation was associated with inferior survival. In HCC, the presence of RP gene mutations, some of which were identical to those previously reported in ribosomopathies, were similarly negatively correlated with long-term survival. Taken together, our results indicate that many if not all cancers possess ribosomopathy-like features that may affect their biological behaviors.
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PMID:Ribosomopathy-like properties of murine and human cancers. 2882 Sep 8

The six-transmembrane epithelial antigen of prostate 2 (STEAP2) protein was identified in advanced prostate cancer, and is highly over-expressed in various types of cancer. This study aimed to investigate the prognostic value and the function of STEAP2 in breast cancer. STEAP2 mRNA and protein expressions in breast normal and cancer tissues, breast cancer cell lines (MCF-7, BT-549, BT-474, MDA-MB-361, HCC1937, and MDA-MB-468) and normal mammary epithelial cell lines (HBL-100 and MCF-10A) were evaluated by immunohistochemistry, real time RT-qPCR and western blotting. The expression of STEAP2 in breast cancer tissues and its value of evaluating the prognosis of breast cancer patients was validated in the Public Databases (Oncomine and Kaplan-Meier plotter database). Lentiviral vectors with STEAP2 cDNA and shRNA were constructed and used to infect breast cancer cell lines and normal mammary epithelial cell line to investigate the effects of STEAP2 up- and down- regulation on the biological behavior of breast cells. The low expression of STEAP2 was detected in breast cancer tissues, which was associated with malignant phenotype and poor prognosis of breast cancer. The public databases analyses were consistent with our findings. STEAP2 up-regulation hindered cellular proliferation, invasion and metastasis abilities by inhibiting EMT process and suppressing PI3K/AKT/mTOR signaling pathway. On the other hand, STEAP2 down-regulation could promote cell proliferation and invasion by inducing EMT and activating the PI3K/AKT/mTOR signaling pathway. Collectively, STEAP2 acted as an anti-oncogene in breast cancer development, which suggested a new research objective for the future studies.
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PMID:STEAP2 is down-regulated in breast cancer tissue and suppresses PI3K/AKT signaling and breast cancer cell invasion in vitro and in vivo. 3169 60