''Zbtb7'', whose protein product is also known as ''Pokemon'', is a

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

that functions as a regulator of cellular growth and a proto oncogene. Zbtb7 is a member of the POK (POZ and Krüppel) family of genes, and the ZBTB protein family that contains

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) which stabilizes the fold. The term ''zinc finger'' was originally coined to describe the finger-like appearance of a ...

and BTB domains. It is also known as LRF10 (leukemia/lymphoma-related factor), OCZF11 (osteoclast-derived zinc finger), and FBI1 (1-3) (fourteen-three-three beta interactant). Zbtb7 is a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

that regulates pathways involved in cell growth and transcription and it specifically represses many activities. When this gene binds to a

consensus sequence In molecular biology and bioinformatics, the consensus sequence (or canonical sequence) is the calculated sequence of most frequent residues, either nucleotide or amino acid, found at each position in a sequence alignment. It represents the result ...

, it prevents transcription by controlling the conformation of

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

and bringing other transcription factors to gene regulation sites. This gene controls access to gene transcription regulation regions. Zbtb7 prevents SP1, a transcription factor, from binding to DNA which will halt the process of transcribing DNA to RNA. Downstream effects of Zbtb7 activity include failure to transcribe ARF, a critical tumor suppressor. Zbtb7 is also involved in the regulation of p53, another tumor suppressor gene. As an oncogene, Zbtb7 is overexpressed in many types of cancer, including lung, liver, prostate, and oral.

Oncogenic studies on Zbtb7

In initial studies using mouse embryonic

fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...

s, researchers found that in the absence of Zbtb7, cellular pathways that convert normal cells into tumor cells did not develop. However, when Zbtb7 was overexpressed, pathways for the transformation of normal cells to cancer cells resulted, both ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' and ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

''. From these observations, researchers concluded that Zbtb7 is often overexpressed in human cancers, and so it can be used to understand biological pathways and patient prognosis. The relationship between Zbtb7 and breast cancer has been investigated. Based on a clinical study, it was concluded that the expression of Zbtb7 is related to the severity of the grade of cancer. High expression of the gene was apparent in patients with grades II and III cancer, while low expression of the gene was found in patients with grade I and II tumors. Zbtb7 can also serve as a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

for patient survival. It was shown that patients with low expression of Zbtb7 were less likely to experience a recurrence in the following five years compared to those with high expression of the gene. Consistent results were concluded in a later study investigating the relationship between Zbtb7 expression and

transitional cell carcinoma Transitional cell carcinoma is a type of cancer that arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs. It typically occurs in the urothelium of the urinary system; in that case, it is also called ...

(TCC) in the bladder. Higher expression of this gene was associated with later stage, more severe grade, higher recurrence, and lower survival. As a result, it is assumed that Zbtb7 expression may be related to the onset, growth, and proliferation of TCC tumors. Researchers stated that some of their data is not statistically significant due to a small sample size and failure to follow-up with patients, so further study is recommended to verify the relationship between Zbtb7 and TCC patient outcomes. Zbtb7 has also been studied in association with renal carcinoma. The study indicated that Zbtb7 was present in abundance in renal carcinoma specimens and that overexpression of the gene was related to increases in cell growth and invasion into other cells and tissues. However, when Zbtb7 was silenced, this activity was not apparent. miR-137, a tumor suppressor

miRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcri ...

was found to decrease the expression of Zbtb7. When Zbtb7 levels increase, it is capable of binding to the promoter region and preventing transcription of miR-137. Together, Zbtb7 and miR-137 form an autoregulatory loop that mediates the onset, growth, and spread of cancer. Zbtb7 is abundantly expressed in

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

(CRC) as well. Treatment for CRC includes administration of

5-Fluorouracil Fluorouracil (5-FU, 5-fluorouracil), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stoma ...

(5-FU),

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

also used to treat other cancers, such as

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

and

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

. Some CRC patients have developed resistance to 5-FU. It has been shown that overexpression of Zbtb7 may increase 5-FU resistance through the NF- appa signaling pathway and thus allow for further proliferation of cancer cells. However, the introduction of SN50, an NF- appa inhibitor reverses resistance caused by Zbtb7. Therefore, the relationship between Zbtb7 and NF- appa may be important in reducing 5-FU resistance in CRC patients.

Etymology

''Pokemon'' is the name given to the protein product of ''Zbtb7'' gene by the research team at

Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a cancer treatment and research institution in Manhattan in New York City. MSKCC is one of 72 National Cancer Institute– designated Comprehensive Cancer Centers. Its main campus is ...

(MSKCC), which discovered its oncogenic function. It stands for "POK erythroid myeloid ontogenic factor" and is most likely a

backronym A backronym is an acronym formed from an already existing word by expanding its letters into the words of a phrase. Backronyms may be invented with either serious or humorous intent, or they may be a type of false etymology or folk etymology. The ...

of the ''Pokémon'' media franchise.

The Pokémon Company , simply known as Pokémon is a Japanese company responsible for brand management, production, publishing, marketing, and licensing of the ''Pokémon'' franchise, which consists of video games, a trading card game, anime television series, f ...

threatened

MSKCC Memorial Sloan Kettering Cancer Center (MSK or MSKCC) is a oncology, cancer treatment and research institution in Manhattan in New York City. MSKCC is one of 72 National Cancer Institute–NCI-designated Cancer Center, designated Comprehen ...

with legal action in December 2005 for creating an association between cancer and the media franchise, and as a consequence

is now referring to it by its gene name ''Zbtb7''.

Genes

* ''

ZBTB7A Zinc finger and BTB domain-containing protein 7A is a protein that in humans is encoded by the ''ZBTB7A'' gene. Interactions ZBTB7A has been shown to Protein-protein interaction, interact with BCL6. See also * ''Zbtb7'' References Further re ...

'' * ''

ZBTB7B Zinc finger and BTB domain-containing protein 7B is a protein that in humans is encoded by the ''ZBTB7B'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of n ...

References

{{Transcription factors, g2 Oncogenes Pokémon