The associated pyrazolopyrimidines PP1 and PP2 inhibit protein tyrosine kinase 6 activity and suppress breast cancer cell proliferation

Shim,Hyun Jae; Kim,Han Ie; Lee,Seung‑Taek

doi:10.3892/ol.2017.5564

The associated pyrazolopyrimidines PP1 and PP2 inhibit protein tyrosine kinase 6 activity and suppress breast cancer cell proliferation

Authors:
- Hyun Jae Shim
- Han Ie Kim
- Seung‑Taek Lee
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Affiliations: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
Published online on: January 2, 2017 https://doi.org/10.3892/ol.2017.5564
Pages: 1463-1469

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Abstract

Protein tyrosine kinase (PTK)6, also known as breast tumor kinase, is a non‑receptor tyrosine kinase. It is closely associated with, but evolutionarily distinct from, the Src family members. PTK6 has a role in proliferation, migration and invasion in various cancers, and therefore has been suggested as a potentially valuable therapeutic target. In an attempt to develop PTK6 inhibitors, chemicals known to inhibit various kinases were screened for their ability to inhibit PTK6. Pyrazolopyrimidine (PP)1, PP2 and a lymphocyte‑specific protein tyrosine kinase inhibitor strongly inhibited the catalytic activity of PTK6 in vitro. These chemicals suppressed the phosphorylation of PTK6 substrate proteins, including signal transducer and activator of transcription 3, in human embryonic kidney (HEK) 293 cells expressing hyperactive PTK6. They also expressed selectivity towards PTK6 over other PTK members in HEK 293 cells. PP1 and PP2 specifically inhibited the PTK6‑dependent proliferation of human breast carcinoma T‑47D cells. PP1 and PP2 were more selective for PTK6 than for Src family kinases, and may be useful for the treatment of PTK6‑positive malignant diseases such as breast cancer.

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