Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic cancer is notoriously becoming one of the most devastating human cancers leading to death. However, clinical challenges still remain in diagnosis and treatment of this ticklish cancer. In the present study, the authors identified a new gene, Tectonic 1 (TCTN1), as a key regulator of cell proliferation in pancreatic cancer. Lentivirus-mediated short hairpin RNA (shRNA) was employed to knock down endogenous TCTN1 expression in PANC-1 pancreatic cancer cells. Knockdown of TCTN1 expression potently inhibited cell viability and proliferation, as determined by MTT and colony formation assays. Western blotting analysis also showed that knockdown of TCTN1 suppressed the expression of cdc2, while it induced that of p21 and p27. Flow cytometry analysis showed that depletion of TCTN1 in PANC-1 cells led to cell cycle arrest in the G2/M phase as well as apoptosis. Besides, depletion of TCTN1 led to the increase of Bax and cleavage of PARP-1, but the decrease of bcl2 by western blotting. The data indicate that TCTN1 is indispensable for pancreatic cancer cell proliferation, which provides a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.
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PMID:Tectonic 1 Is a Key Regulator of Cell Proliferation in Pancreatic Cancer. 2684 47

BACKGROUND Tectonic family member 1 (TCTN1), a member of the tectonic family, is involved in several developmental processes and is aberrantly expressed in multiple solid tumors. However, the expression and regulation of TCTN1 in human colorectal cancer (CRC) is still not clear. MATERIAL AND METHODS The expression of TCTN1 mRNA was first explored by using Oncomine microarray datasets. TCTN1 expression was silenced in human CRC cell lines HCT116 and SW1116 via RNA interference (RNAi). Furthermore, we investigated the effect of TCTN1 depletion on CRC cell growth by MTT, colony formation, and flow cytometry in vitro. RESULTS In this study, meta-analysis showed that the expressions of TCTN1 mRNA in CRC specimens were significantly higher than that in normal specimens. Knockdown of TCTN1 expression potently inhibited the abilities of cell proliferation and colony formation as determined. Flow cytometry analysis showed that depletion of TCTN1 could cause cell cycle arrest at the G2/M phase. In addition, Annexin V/7-AAD double-staining indicated that TCTN1 silencing promoted cell apoptosis through down-regulation of caspase 3 and Bcl-2 and upregulation of cleaved caspase 3 and PARP. CONCLUSIONS Our results indicate that TCTN1 may be crucial for CRC cell growth, providing a novel alternative to target therapies of CRC. Further research on this topic is warranted.
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PMID:Knockdown of TCTN1 Strongly Decreases Growth of Human Colon Cancer Cells. 2812 72

Tectonic family member 1 (TCTN1) is one of the tectonic family members, and a regulator of the hedgehog signaling pathway, which has been studied in various cancer types, including prostate and pancreatic cancer. However, its function in thyroid cancer has not been well documented. Therefore, the present study investigated the function of TCTN1 in thyroid cancer using a loss-of-function assay. Lentivirus-mediated RNA interference was applied to downregulate TCTN1 in the thyroid cancer cell lines, CAL62 and 8305C. A series of functional properties, including cell viability, colony formation, cell cycle and apoptosis were determined using MTT, colony formation assay and flow cytometry analyses, respectively. The results demonstrated that lentivirus-medicated RNAi could specifically suppress the expression of TCTN1 at the mRNA and protein levels in CAL62, and 8305C cells. Knockdown of TCTN1 inhibited cell growth and proliferation via inducing S phase arrest, and apoptosis. Mechanistically, the S phase arrest was accompanied by the upregulation of cyclin dependent kinase 2, cyclin A2 and downregulation of cyclin B1. Knockdown of TCTN1 induced apoptosis through increasing the expression of Bcl2-associated agonist of cell death, cleaved caspase-3 and poly(ADP-ribose)polymerase, and decreasing apoptosis regulator Bcl-2 expression. The current study highlights the essential role of TCTN1 in promoting thyroid cancer cell proliferation, and its knockdown may serve as a potential therapeutic treatment for thyroid cancer.
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PMID:Silencing of TCTN1 inhibits proliferation, induces cell cycle arrest and apoptosis in human thyroid cancer. 2904 69

Tctn3 belongs to the Tectonic (Tctn) family and is a single-pass membrane protein localized at the transition zone of primary cilia as an important component of ciliopathy-related protein complexes. Previous studies showed that mutations in Tctn1 and Tctn2, two members of the tectonic family, have been reported to disrupt neural tube development in humans and mice, but the functions of Tctn3 in brain development remain elusive. In this study, Tctn3 knockout (KO) mice were generated by utilizing the piggyBac (PB) transposon system. We found that Tctn3 KO mice exhibited abnormal global development, including prenatal lethality, microphthalmia, polysyndactyly, and abnormal head, sternum, and neural tube, whereas Tctn3 heterozygous KO mice did not show abnormal development or behaviors. Further, we found that the mRNA levels of Gli1 and Ptch1, downstream signaling components of the Shh pathway, were significantly reduced. Likewise, neural tube patterning-related proteins, such as Shh, Foxa2, and Nkx2.2, were altered in their distribution. Interestingly, Tctn3 KO led to significant changes in apoptosis-related proteins, including Bcl-2, Bax, and cleaved PARP1, resulting in reduced numbers of neuronal cells in embryonic brains. Tctn3 KO inhibited the PI3K/Akt signaling pathway but not the mTOR-dependent pathway. The small molecule SC79, a specific Akt activator, blocked apoptotic cell death in primary mouse embryonic fibroblasts from Tctn3 KO mice. Finally, NPHP1, a protein with anti-apoptotic ability, was found to form a complex with Tctn3, and its levels were decreased in Tctn3 KO mice. In conclusion, our results show that Tctn3 KO disrupts the Shh signaling pathway and neural tube patterning, resulting in abnormal embryonic development, cellular apoptosis, and prenatal death in mice.
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PMID:Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice. 2972 84