Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma

Zane Hammoud, Bailin Tan, Sunil Badve, Robert Bigsby

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Numerous epidemiological observations point to sex differences in lung cancer etiology and progression. The present study was aimed at understanding the bases of these sex differences. To test the effect of estradiol on tumor progression, we used a mouse model based on conditional Kras expression and concurrent deletion of Tp53 following inhalation of an adenoviral vector expressing Cre recombinase (AdeCre). Ovariectomized females and males were treated with estradiol via a continuous-release capsule. Tumor multiplicity, tumor volume, and histological grade were determined at 10 weeks after AdeCre administration. Cell proliferation was monitored by Ki67 immunohistochemistry at 4 and 10 weeks after AdeCre administration. At 10 weeks, female mice had more than twice the number of tumors evident on the surface of the lungs than male mice; ovariectomy eliminated this sex difference. The estrogen treatment significantly increased tumor number and volume in ovariectomized females and in males. Histological character of the tumors ranged from adenoma to adenocarcinoma. Ovary-intact females exhibited higher grade tumors than ovariectomized females or males. Progression to higher histological grade was stimulated by estrogen in male mice but not in ovariectomized females. At 10 weeks after AdeCre administration, tumor cell Ki67-labeling varied widely, precluding assessment of an estrogen effect; however, at 4 weeks, Ki67 labeling of lung parenchymal cells was increased 3.5-fold by estrogen. In conclusion, estrogen acts as a promoter for lung adenocarcinoma in a genetically defined lung cancer model; estrogen-induced cell proliferation in the oncogene-initiated cells is likely to play a role in this tumor promoter activity.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalEndocrine-Related Cancer
Volume15
Issue number2
DOIs
StatePublished - Jun 2008

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Estrogens
Sex Characteristics
Neoplasms
Tumor Burden
Estradiol
Lung Neoplasms
Cell Proliferation
Lung
Ovariectomy
Oncogenes
Carcinogens
Adenoma
Inhalation
Capsules
Adenocarcinoma of lung
Ovary
Adenocarcinoma
Immunohistochemistry
Cre recombinase
Therapeutics

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen promotes tumor progression in a genetically defined mouse model of lung adenocarcinoma. / Hammoud, Zane; Tan, Bailin; Badve, Sunil; Bigsby, Robert.

In: Endocrine-Related Cancer, Vol. 15, No. 2, 06.2008, p. 475-483.

Research output: Contribution to journalArticle

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