Effect of sialoadenectomy on medroxyprogesterone-acetate-induced mammary carcinogenesis in BALB/c mice. Correlation between histology and epidermal-growth-factor receptor content.
To evaluate the possible involvement of the salivary glands in the modulation of medroxyprogesterone (MPA)-induced mammary tumorigenesis, 48 sialoadenectomized virgin BALB/c female mice and 47 controls were treated with 40mg MPA depot s.c. every 3 months for 1 year. Mammary tumors developed in 11 sialoadenectomized and in 34 control mice with similar latencies. In both groups, 75% of the tumors were ductal and progestin-dependent (PD) while the remainder were lobular and progestin-independent (PI). Epidermal growth factor (EGF) levels were measured in salivary glands (SG-EGF) and serum (S-EGF) in both groups. MPA induced a significant increase in SG-EGF and in S-EGF that became evident only after 1 month of MPA treatment. No increase in S-EGF was detected in MPA-treated sialoadenectomized mice, indicating that salivary glands are the major source of S-EGF. The presence of EGF receptors (EGF-R) was investigated in ductal PD and PI tumor lines and compared with 8 PI tumor lines of lobular origin. A significant difference in EGF-R content was found between lobular and ductal tumors. No increase in EGF-R was noted when ductal tumors became autonomous. EGF-R did not correlate with tumor growth rate and there was an inverse correlation between EGF-R and steroid receptors. When the effect of sialoadenectomy on tumor growth was tested in vivo in syngeneic transplants of 2 ductal PD, 1 ductal PI and 2 lobular PI mammary adenocarcinomas, it was not found to be significant when compared with the controls. It may be concluded that SG-EGF plays an important role in the induction of mammary adenocarcinomas by MPA, while it has no significant effect on the growth of established tumors.
Kordon
E C
EC
División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
Guerra
F
F
Molinolo
A A
AA
Elizalde
P
P
Charreau
E H
EH
Pasqualini
C D
CD
Montecchia
F
F
Pazos
P
P
Dran
G
G
Lanari
C
C
D000818:Animals; D002455:Cell Division / Q000502:physiology; D004815:Epidermal Growth Factor / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology* / Q000648:ultrastructure; D017258:Medroxyprogesterone Acetate / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced* / Q000473:pathology* / Q000648:ultrastructure; D012469:Salivary Glands / Q000378:metabolism / Q000502:physiology* / Q000601:surgery
D004815:Epidermal Growth Factor; D017258:Medroxyprogesterone Acetate; D066246:ErbB Receptors