Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A relatively new view of colorectal cancer is that its development/progression reflects the contribution of a large set of altered gene products in varying combinations, each providing a "fitness advantage." In searching for novel contributing gene products using Unigene cluster data mining, we found overrepresentation of expressed sequence tags corresponding to a previously uncharacterized gene (ZKSCAN3) in colorectal tumors. ZKSCAN3 was pursued for several reasons: (a) its sequence similarity with bowl required for Drosophila hindgut development; (b) it lies in a chromosomal region (6p22.1) amplified in colorectal cancer; and (c) its coding sequence predicts tandem C(2)H(2) zinc finger domains present in a class of proteins gaining attention for their role in oncogenesis/tumor progression. Reverse transcription-PCR confirmed overexpression in colorectal tumor tissue compared with adjacent nonmalignant mucosa due in part to gene amplification determined by Southern blotting. Further, immunohistochemistry with an antibody generated to the predicted protein sequence revealed higher ZKSCAN3 expression in invasive compared with noninvasive tumors. Intriguingly, the ZKSCAN3 protein was also expressed in tumors wild-type for genes (APC, p53, K-Ras) commonly targeted in colorectal cancer. ZKSCAN3 knockdown in two independent colon cancer cell lines impaired anchorage-independent growth and orthotopic tumor growth, whereas overexpression in a third cell line had the opposite effect and increased 5-fluorouracil resistance. Liposomal delivery of a ZKSCAN3-targeting small interfering RNA reduced tumorigenicity of orthotopic colon cancer. Thus, the hitherto uncharacterized ZKSCAN3 adds to an expanding set of encoded products contributing to the progression of colorectal cancer.
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PMID:The previously undescribed ZKSCAN3 (ZNF306) is a novel "driver" of colorectal cancer progression. 1851 92

ZKSCAN3, a zinc-finger transcription factor, which has been shown to be upregulated in several human cancer. However, the expression level, function and mechanism of ZKSCAN3 in breast cancer remains unknown. In the current study, immunohistochemistry, western blot and quantitative real time polymerase chain reaction (qRT-PCR) results showed that ZKSCAN3 was overexpressed in breast cancer tissue compared with normal breast tissue. Through analyzing the clinicopathological characteristics, we demonstrated that positive ZKSCAN3 expression predicted poor prognosis of patients with breast cancer. The expression level of ZKSCAN3 protein/mRNA in breast cancer cells (MCF-7 and MDA-MB-231) was higher than its expression in normal breast cells (HBL-100). Knocking down ZKSCAN3 via its short hairpin RNA (shRNA) in MCF-7 and MDA-MB-231 inhibited cell viability, migration and invasion. Western blot analysis showed that ZKSCAN3 silencing lead to significant decreases in the expression of Cyclin D1, B-cell lymphoma-2 (Bcl-2), and matrix metalloproteinase (MMP)-2/MMP-9, as well as increases in the expression of Bcl2 Associated X Protein (Bax) in breast cancer cells. Additionally, ZKSCAN3-shRNA expression markedly suppressed tumor growth in breast cancer xenograft mice. Finally, we demonstrated that silencing of ZKSCAN3 was able to inhibit Akt/mTOR signaling pathway by blocking p-Akt and p-mTOR protein expression in breast cancer cells. These results demonstrate that ZKSCAN3 plays a significant role in the progression of breast cancer. Therefore, ZKSCAN3 is a potential therapeutic target for breast cancer.
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PMID:ZKSCAN3 promotes breast cancer cell proliferation, migration and invasion. 3004 38