Advanced rat mammary cancers are growth hormone dependent.

Abstract

Epidemiological studies suggest that the GH/IGF-I axis may promote human cancers. Animal models in which the GH/IGF-I axis can be controlled may be helpful in elucidating the role of these hormones during mammary cancer progression. Beginning at 3 or 5 wk of age, spontaneous dwarf rats (Gh(dr/dr)), which lack GH and have very low serum IGF-I, were treated with either rat or bovine GH twice daily. Other Gh(dr/dr) rats received vehicle, and wild-type Sprague Dawley rats (Gh(+/+), parent strain to SDR) received vehicle. One week later, all rats were exposed to a single injection of N-methyl-N-nitrosourea. Body weight gain and serum IGF-I levels were similar in Gh(+/+) and GH-treated Gh(dr/dr) rats. Furthermore, mammary tumor incidence, latency, and multiplicity were similar in Gh(+/+) and GH-treated Gh(dr/dr) rats. Vehicle-treated Gh(dr/dr) rats developed no tumors. Once advanced (> or =1 cm(3)) mammary cancers were established in GH-treated Gh(dr/dr) rats, GH treatments were halted and nearly all tumors regressed completely within 2 wk. Tumor regression was associated with loss of phospho-signal transducer and activator of transcription-3, but not alterations in IGF-I, IGF-I receptor, or GH receptor. These results demonstrate that Gh(dr/dr) rats, which are nearly refractory to mammary carcinogenesis, can be made vulnerable by restoring GH and IGF-I. Furthermore, advanced rat mammary cancers are dependent on GH and/or IGF-I for their survival. Therefore, therapeutics that target either GH or IGF-I may be effective at treating even advanced mammary cancers.

• Authors: Qi Shen, Daniel D Lantvit, Qing Lin, Yongjun Li, Konstantin Christov, Zhuohua Wang, Terry G Unterman, Rajendra G Mehta, Steven M Swanson
• Journal: Endocrinology (Endocrinology) Vol. 148 Issue 10 Pg. 4536-44 (Oct 2007) ISSN: 0013-7227 [Print] United States
• PMID: 17584969 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• growth hormone, bovine
• Insulin-Like Growth Factor I
• Methylnitrosourea
• Growth Hormone

Topics

• Animals
• Disease Susceptibility
• Drug Administration Schedule
• Dwarfism (blood, genetics, metabolism, physiopathology)
• Growth Hormone (administration & dosage, deficiency)
• Insulin-Like Growth Factor I (deficiency, metabolism)
• Mammary Neoplasms, Experimental (chemically induced, pathology)
• Methylnitrosourea
• Rats
• Rats, Mutant Strains
• Rats, Sprague-Dawley
• Remission Induction