Transgenic mice overexpressing hepatocyte growth factor in the airways show increased susceptibility to lung cancer

Carcinogenesis
Laura P StabileJill M Siegfried

Abstract

Several studies have suggested a possible role of the hepatocyte growth factor (HGF)/c-Met system in lung tumor development and progression. Extent of expression of both HGF and c-Met have been shown to be negative prognostic indicators of survival and recurrence in non-small-cell lung cancer, especially adenocarcinoma. To further define a role for HGF in lung cancer development and growth, we have generated transgenic mice that overexpress HGF in the airway epithelium. HGF transgenic and wild-type mice were exposed to the tobacco carcinogen, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), or saline control and killed 10-38 weeks after exposure. Lungs were formalin inflated, paraffin embedded and sectioned. It was verified that the HGF transgene was expressed only in the lungs of transgenic mice. The transgenic mouse lung histology exhibited congestion in the alveolar spaces, excess production of blood vessels and a convoluted pattern of airways with wide bifurcations. The number of lung tumors from NNK-treated transgenic animals versus the number of lung tumors from NNK-treated wild-type animals was significantly higher (P = 0.0001, Poisson regression). The percentage of animals with tumors was 75% in the tra...Continue Reading

Citations

Aug 4, 2012·Carcinogenesis·Laura P StabileJill M Siegfried
May 31, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hai XuJill M Siegfried
Sep 10, 2011·Therapeutic Advances in Medical Oncology·Martin SattlerRavi Salgia
Jan 9, 2013·International Journal of Molecular Sciences·Shinya Mizuno, Toshikazu Nakamura
May 12, 2011·Journal of Oncology·Hua-Chuan Zheng, Yasuo Takano
Mar 24, 2017·Yonsei Medical Journal·Jun PeiBaohui Han
Feb 10, 2007·Current Oncology Reports·Martin Sattler, Ravi Salgia
Jun 30, 2007·Molekuliarnaia genetika, mikrobiologiia i virusologiia·I V KorobkoE D Svwrdlov
May 29, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Terumi TakaharaPaolo Michieli
Feb 20, 2018·Molecular Cancer·Qian LiuKongming Wu
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Jan 17, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chih-Ching ChangChun-Yuh Yang
Jul 14, 2020·Cancer Prevention Research·Christian NjatchaJill M Siegfried
Apr 7, 2010·Update on Cancer Therapeutics·Martin Sattler, Ravi Salgia

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