Disrupting a Tumor Suppressor Actually Confers Resistance to Cancer Growth

Cancer researchers have found that protein tyrosine kinase 6 (PTK6), which was thought to suppress growth of colon cancer cells, actually promotes tumor growth and development.

Protein tyrosine kinase 6 (PTK6) is expressed throughout the gastrointestinal tract and is a negative regulator of proliferation that promotes differentiation and DNA damage-induced apoptosis in the small intestine. PTK6 is not expressed in normal mammary gland, but is induced in most human breast tumors. A different protein, signal transducer and activator of transcription 3 (STAT3), mediates pathogenesis of colon cancer and is a substrate of PTK6. To understand the role of PTK6 in breast cancer tumorigenesis better, investigators at the University of Illinois (Chicago, USA) genetically engineered a line of mice to lack the gene that encodes PTK6.

The genetically engineered mice and a group of normal control mice were injected with the carcinogen azoxymethane alone or in combination with dextran sodium sulfate. The effects of disruption of PTK6 on proliferation, apoptosis, and STAT3 activation were examined by immunoblot and immunohistochemical analyses. Regulation of STAT3 activation was examined in the HCT116 colon cancer-cell line and in young adult mouse colon cells.

Results published in the October 2011 issue of the journal Gastroenterology revealed that disruption of PTK6 decreased azoxymethane-induced colon tumorigenesis in mice. The molecular basis for this decrease was that the lack of PTK6 reduced STAT3 activity in the mouse colon cells. Failure of PTK6 to activate STAT3 was tumor suppressive. When PTK6 was induced in the azoxymethane treated genetically engineered mice, the result was increased apoptosis, proliferation, and STAT3 activation.

“Our research has primarily focused on the normal function of this protein in the gut, where it regulates growth and differentiation,” said senior author Dr. Angela Tyner, professor of biochemistry and molecular genetics at the University of Illinois. “Mice lacking PTK6 were highly resistant to the carcinogen and developed fewer tumors. It was an unexpected result. We believe that PTK6 may play a role in initiation of cancer in the colon, but we don't yet know what role PTK6 may play in metastasis.”

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