Accumulation of albumin in renal cytosol of hamsters treated with estradiol and in estrogen-induced hamster kidney tumors.
The intracellular accumulation of albumin has been observed in cytosols of benign and malignant human breast tumors and in mammary tumors of rodents induced by carcinogens. Additionally, cellular uptake of albumin has been detected in MCF-7 human breast cancer cells in culture. The clinical relevance of the albumin accumulation in human and rodent mammary tumors is not clear. In this study, we investigated the accumulation of albumin in an estrogen-induced and -dependent hamster kidney tumor model to understand the mechanisms and the role of hormones in this process. Protein accumulation patterns were examined by Western blot analyses in kidney homogenates of hamsters treated with 17beta-estradiol for various lengths of time and in kidney tumors which are induced with 100% incidence by this treatment for at least six months. Such analyses were also carried out in tissues of hamsters treated with the weakly carcinogenic estrogen 17alpha-ethinylestradiol (10% tumor incidence after nine months of treatment). Our data demonstrate the accumulation of albumin in kidney of hamsters treated with 17beta-estradiol but not with 17alpha-ethinylestradiol. Albumin accumulates specifically in the target organ of carcinogenesis, the kidney, however, with no increase in the serum concentrations or in the liver. Tumors do not develop in the livers of hamsters under these conditions of 17beta-estradiol treatment. This accumulation of albumin in hamster kidney may be the result of damage to the glomerulum which may be compromised by estradiol-induced toxicity and therefore unable to filter out excess albumin.
Division of Laboratory Research and Development, Department of Medicine, Charles R. Drew University of Medicine and Science, Hawkins Building MP30, Los Angeles, CA 90059, USA.
H K
HK
Bhat
J V
JV
Vadgama
J G
JG
Liehr
D000595:Amino Acid Sequence; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D006224:Cricetinae; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens; D004997:Ethinyl Estradiol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012709:Serum Albumin / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D012709:Serum Albumin; D004997:Ethinyl Estradiol; D004958:Estradiol