Zbtb7

Oncogenic studies on Zbtb7

In initial studies using mouse embryonic fibroblasts, 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 and in vivo. 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 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 (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 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 (CRC) as well. Treatment for CRC includes administration of 5-Fluorouracil (5-FU), chemotherapy also used to treat other cancers, such as pancreatic cancer and breast cancer. 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-[kappa]B signaling pathway and thus allow for further proliferation of cancer cells. However, the introduction of SN50, an NF-[kappa]B inhibitor reverses resistance caused by Zbtb7. Therefore, the relationship between Zbtb7 and NF-[kappa]B 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 (MSKCC), which discovered its oncogenic function. It stands for "POK erythroid myeloid ontogenic factor" and is most likely a backronym of the Pokémon media franchise. The Pokémon Company threatened MSKCC with legal action in December 2005 for creating an association between cancer and the media franchise, and as a consequence MSKCC is now referring to it by its gene name Zbtb7.

Genes

• ZBTB7A
• ZBTB7B

References

References

1. (2005). "The Transcription Factor ''Pokemon'': A New Key Player in Cancer Pathogenesis". Cancer Research.
2. (October 2017). "The expression and clinical significance of ZBTB7 in transitional cell carcinoma of the bladder". Oncology Letters.
3. (15 September 1999). "Osteoclast-derived zinc finger (OCZF) protein with POZ domain, a possible transcriptional repressor, is involved in osteoclastogenesis.". Blood.
4. "FBI1 (Human)".
5. (February 2014). "FBI1/Akirin2 promotes tumorigenicity and metastasis of Lewis lung carcinoma cells". Biochemical and Biophysical Research Communications.
6. (23 March 2012). "Zbtb7 suppresses the expression of CDK2 and E2F4 in liver cancer cells: Implications for the role of Zbtb7 in cell cycle regulation". Molecular Medicine Reports.
7. "ZBTB7A - Zinc finger and BTB domain-containing protein 7A - Homo sapiens (Human) - ZBTB7A gene & protein".
8. (2018-08-10). "ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF‑κB signaling pathway". International Journal of Oncology.
9. (January 2005). "Role of the proto-oncogene Pokemon in cellular transformation and ARF repression". Nature.
10. (June 2010). "ZBTB7 Overexpression Contributes to Malignancy in Breast Cancer". Cancer Investigation.
11. (October 2017). "The expression and clinical significance of ZBTB7 in transitional cell carcinoma of the bladder". Oncology Letters.
12. (2019-09-23). "ZBTB7/miR-137 Autoregulatory Circuit Promotes the Progression of Renal Carcinoma". Oncology Research.
13. Spelled like this in the original article; likely a misspelling of ''on'''c'''ogenic''
14. Brendan Sinclair. (2005-12-19). "Pokémon USA threatens to sue cancer researchers". [[GameSpot]].