ABSTRACT Gene amplification is common in solid tumors and is associated with adverse prognosis, disease progression, and development of drug resistance. A small segment from chromosome

17q11–12 containing the _HER-2/Neu_ gene is amplified in about 25% of breast cancer. _HER-2/Neu_ amplification is associated with adverse prognosis and may predict response to chemotherapy

and hormonal manipulation. Moreover, _HER-2/Neu_ amplification may select patients for anti-_HER-2/Neu_-based therapy with Herceptin. We and others recently described a common sequence

element from the _HER-2/Neu_ region that was amplified in breast cancer cells. In addition, most, if not all, of the amplified genes from this region display overexpression. This raises the

phosphotidylinositol phosphate kinase (PIPK), _Pip4k2β_ from 17q11–12. Although a role of PI-3-kinase and AKT in cancer biology has been previously described, PIPK has not been previously

implicated. We show that _Pip4k2β_, initially known as _Pip5k2β_, is amplified in a subset of breast cancer cell lines and primary breast cancer samples that carry _HER-2/Neu_ amplification.

Out of eight breast cancer cell lines with _HER-2/Neu_ amplification, three have concomitant amplification of the _Pip4k2β_ gene – UACC-812, BT-474 and ZR-75-30. Similarly, two out of four

primary breast tumors with _HER-2/Neu_ amplification carry _Pip4k2β_ gene amplification. Intriguingly, one tumor displays an increase in the gene copy number of _Pip4k2β_ that is

significantly more than that of _HER-2/Neu_. Moreover, dual color FISH reveals that amplified _Pip4k2β_ gene may exist in a distinct structure from that of _HER-2/Neu_ in ZR-75-30 cell line.

These studies suggest that _Pip4k2β_ may reside on an amplification maximum distinct from that of _HER-2/Neu_ and serve as an independent target for amplification and selective retention.

_Pip4k2β_ amplification is associated with overexpression at the RNA and protein level in breast cancer cell lines. Stable expression of _Pip4k2β_ in breast cancer cell lines with and

without _HER-2/Neu_ amplification increases cell proliferation and anchorage-independent growth. The above observations implicate _Pip4k2β_ in the development and/or progression of breast

cancer. Our study suggests that _Pip4k2β_ may be a distinct target for gene amplification and selective retention from 17q11–12. Access through your institution Buy or subscribe This is a

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TRANSLOCATIONS UNDERLIE ONCOGENE AMPLIFICATIONS IN BREAST CANCER Article Open access 17 May 2023 CHROMOTHRIPSIS FOLLOWED BY CIRCULAR RECOMBINATION DRIVES ONCOGENE AMPLIFICATION IN HUMAN

CANCER Article 15 November 2021 _CDK4_ IS CO-AMPLIFIED WITH EITHER _TP53_ PROMOTER GENE FUSIONS OR _MDM2_ THROUGH DISTINCT MECHANISMS IN OSTEOSARCOMA Article Open access 25 September 2024

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mentorship and support. We thank Drs Bob Franco, Tom Clemans, Jeff Kanuf, and Peter Stambrook for careful review of the manuscripts. S-WL was a recepient of Fellow Scholarship from American

Society of Hematology. This paper is dedicated to the loving memory of late Dr Ching-Shuenn Luoh. AUTHOR INFORMATION Author notes * Shiuh-Wen Luoh: Supported in part by American Cancer

Society, Ohio Chapter, Ohio Cancer Research Associates, and VA Merit Award AUTHORS AND AFFILIATIONS * Department of Medicine, Division of Hematology and Oncology, University of Cincinnati,

College of Medicine, Cincinnati, 45267, OH, USA Shiuh-Wen Luoh & Reshimi Tripathi * Cincinnati Veterans' Affairs Medical Center Cincinnati, Cincinnati, 45220, OH, USA Shiuh-Wen Luoh

* Division of Hematology and Oncology, Department of Medicine, UCLA Medical Center, Los Angeles, 90095, CA, USA Natarajan Venkatesan Authors * Shiuh-Wen Luoh View author publications You

can also search for this author inPubMed Google Scholar * Natarajan Venkatesan View author publications You can also search for this author inPubMed Google Scholar * Reshimi Tripathi View

author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Luoh, SW., Venkatesan, N.

& Tripathi, R. Overexpression of the amplified _Pip4k2β_ gene from 17q11–12 in breast cancer cells confers proliferation advantage. _Oncogene_ 23, 1354–1363 (2004).

https://doi.org/10.1038/sj.onc.1207251 Download citation * Received: 26 June 2003 * Revised: 04 September 2003 * Accepted: 29 September 2003 * Published: 22 December 2003 * Issue Date: 19

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gene amplification * gene expression * _HER-2/Neu_