Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002.

Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Research Abstract Details 

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Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Abstract Text:

Muthusamy Kunnimalaiyaan,Mary Ndiaye,Herbert Chen,

BACKGROUND: Medullary thyroid cancer (MTC) cells exhibit frequent activation of the PI3K pathway as evidenced by the presence of hyperactivation of Akt kinases and overexpression of neuroendocrine (NE) markers. We hypothesized that the inhibition of the PI3K pathway in MTC may lead to a reduction in cell growth and NE tumor marker production. METHODS: Human MTC-TT cells were treated with the PI3K inhibitor LY294002 (0-60 micromol/L) for 8 days, and cellular growth was measured. Further, TT cells were treated with nontoxic concentrations of LY294002 for 2 days, and Western blot analyses were performed for phospho-Akt, total Akt, and the NE tumor markers CgA and human achaete-scute homolog1 (ASCL1). RESULTS: Treatment of TT cells with LY294002 significantly suppressed levels of phospho-Akt. Notably, a dose-dependent reduction in cellular proliferation was also observed. Importantly, NE marker production was also reduced. Mechanistically, we show that cell growth inhibition by PI3K inactivation is mediated by apoptosis attributable to an increase in the levels of cleaved poly(ADP-ribose) polymerase and caspase-3. CONCLUSIONS: MTC cell growth and NE marker production appear to depend on activation of the PI3K-signaling cascade. Inhibition of this important signal transduction pathway may lead to a possible therapeutic strategy to treat patients with MTC.

Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Publishing Authors By Initials

M Kunnimalaiyaan,M Ndiaye,H Chen,

For similar neoplasms: neoplasms by site: endocrine gland neoplasms: thyroid neoplasms research abstracts see: neoplasms: neoplasms by site: endocrine gland neoplasms: thyroid neoplasms research

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Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Surgery

VOLUME: 140

Page Numbers: 1009-14; discussion 1014-5

Journal Abbreviation: Surgery

ISSN: 0039-6060

DAY: 1

MONTH: 11

YEAR: 2006

Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 417347

Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Keywords Mesh Terms:

KEYWORDS: Thyroid Neoplasms

MESH TERMS: pathology

Chemical & Substance for Abstract: Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002. Information

Substance Name: Caspase 3

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K inhibitor LY294002.

AFFILIATION: Department of Surgery, Section of Endocrine Surgery, Endocrine Surgery Research Laboratories, The University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: R21-DK066169

ACRONYM: DK

MEDLINETA: Surgery

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