The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer

Il Man Kim, Timothy Ackerson, Sneha Ramakrishna, Maria Tretiakova, I. Ching Wang, Tanya V. Kalin, Michael L. Major, Galina A. Gusarova, Helena M. Yoder, Robert H. Costa, Vladimir V. Kalinichenko

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Abstract

The proliferation-specific Forkhead Box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) regulates expression of cell cycle genes essential for progression into DNA replication and mitosis. Expression of Foxm1 is found in a variety of distinct human cancers including hepatocellular carcinomas, intrahepatic cholangiocarcinomas, basal cell carcinomas, ductal breast carcinomas, and anaplastic astrocytomas and glioblastomas. In this study, we show that human Foxm1 protein is abundantly expressed in highly proliferative human non-small cell lung cancers (NSCLC) as well as in mouse lung tumors induced by urethane. To determine the role of Foxm1 during the development of mouse lung tumors, we used IFN-inducible Mx-Cre recombinase transgene to delete mouse Foxm1 f1/f1-targeted allele before inducing lung tumors with urethane. We show that Mx-Cre Foxm1-/- mice exhibit diminished proliferation of lung tumor cells causing a significant reduction in number and size of lung adenomas. Transient transfection experiments with A549 lung adenocarcinoma cells show that depletion of Foxm1 levels by short interfering RNA caused diminished DNA replication and mitosis and reduced anchorage-independent growth of cell colonies on soft agar. Foxm1-depleted A549 cells exhibit reduced expression of cell cycle-promoting cyclin A2 and cyclin B1 genes. These data show that Foxm1 stimulates the proliferation of tumor cells during progression of NSCLC.

Original languageEnglish (US)
Pages (from-to)2153-2161
Number of pages9
JournalCancer Research
Volume66
Issue number4
DOIs
StatePublished - Feb 15 2006

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Forkhead Transcription Factors
Lung Neoplasms
Cell Proliferation
Lung
Neoplasms
Urethane
DNA Replication
Mitosis
Non-Small Cell Lung Carcinoma
Cyclin A2
Carcinoma, Ductal, Breast
Cyclin B1
cdc Genes
Ductal Carcinoma
Cholangiocarcinoma
Basal Cell Carcinoma
Astrocytoma
Glioblastoma
Transgenes
Adenoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kim, I. M., Ackerson, T., Ramakrishna, S., Tretiakova, M., Wang, I. C., Kalin, T. V., ... Kalinichenko, V. V. (2006). The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Research, 66(4), 2153-2161. https://doi.org/10.1158/0008-5472.CAN-05-3003

The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. / Kim, Il Man; Ackerson, Timothy; Ramakrishna, Sneha; Tretiakova, Maria; Wang, I. Ching; Kalin, Tanya V.; Major, Michael L.; Gusarova, Galina A.; Yoder, Helena M.; Costa, Robert H.; Kalinichenko, Vladimir V.

In: Cancer Research, Vol. 66, No. 4, 15.02.2006, p. 2153-2161.

Research output: Contribution to journalArticle

Kim, IM, Ackerson, T, Ramakrishna, S, Tretiakova, M, Wang, IC, Kalin, TV, Major, ML, Gusarova, GA, Yoder, HM, Costa, RH & Kalinichenko, VV 2006, 'The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer', Cancer Research, vol. 66, no. 4, pp. 2153-2161. https://doi.org/10.1158/0008-5472.CAN-05-3003
Kim, Il Man ; Ackerson, Timothy ; Ramakrishna, Sneha ; Tretiakova, Maria ; Wang, I. Ching ; Kalin, Tanya V. ; Major, Michael L. ; Gusarova, Galina A. ; Yoder, Helena M. ; Costa, Robert H. ; Kalinichenko, Vladimir V. / The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. In: Cancer Research. 2006 ; Vol. 66, No. 4. pp. 2153-2161.
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