Abstract
Transforming growth factors-β (TGFβ) are a family of closely related, ubiquitously expressed growth factors with the common properties of induction of growth inhibition and expression of differentiation-related markers in epithelial cells. We investigated the role of TGFβ1 in growth regulation of normal human mammary epithelial cells and in benzo(a)pyrene immortalized sublines further transformed by oncogenes in retroviral vectors. The normal cells were markedly growth inhibited by TGFβ1, produced TGFβ in a latent form, and expressed TGFβ receptors. In the immortalized cells, both TGFβ-induced growth inhibition and TGFβ receptor binding were reduced. With the single oncogenes v-Ha-ras, v-mos, and SV40 T, growth sensitivity to TGFβ1 increased, but TGFβ production or TGFβ receptor expression was not altered. Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGFβ under anchorage-independent, but not anchorage-dependent, conditions without affecting TGFβ production or receptor characteristics. Thus, modulation of TGFβ growth responsiveness in these normal and oncogene transformed human mammary epithelial cells apparently occurs at a level distal to TGFβ receptor binding and is not solely correlated to expression of transforming oncogenes. Further, modulation of TGFβ production is not an indicator of malignant transformation in this system.
| Original language | English |
|---|---|
| Pages (from-to) | 6269-6274 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 49 |
| Issue number | 22 |
| State | Published - Jan 1 1989 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Production of and responsiveness to transforming growth factor-β in normal and oncogene-transformed human mammary epithelial cells. / Valverius, E. M.; Lippman, Marc E; Bates, S. E.; Stampfer, M. R.; Clark, R.; McCormick, F.; Dickson, R. B.; Lippman, M. E.
In: Cancer Research, Vol. 49, No. 22, 01.01.1989, p. 6269-6274.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Production of and responsiveness to transforming growth factor-β in normal and oncogene-transformed human mammary epithelial cells
AU - Valverius, E. M.
AU - Lippman, Marc E
AU - Bates, S. E.
AU - Stampfer, M. R.
AU - Clark, R.
AU - McCormick, F.
AU - Dickson, R. B.
AU - Lippman, M. E.
PY - 1989/1/1
Y1 - 1989/1/1
N2 - Transforming growth factors-β (TGFβ) are a family of closely related, ubiquitously expressed growth factors with the common properties of induction of growth inhibition and expression of differentiation-related markers in epithelial cells. We investigated the role of TGFβ1 in growth regulation of normal human mammary epithelial cells and in benzo(a)pyrene immortalized sublines further transformed by oncogenes in retroviral vectors. The normal cells were markedly growth inhibited by TGFβ1, produced TGFβ in a latent form, and expressed TGFβ receptors. In the immortalized cells, both TGFβ-induced growth inhibition and TGFβ receptor binding were reduced. With the single oncogenes v-Ha-ras, v-mos, and SV40 T, growth sensitivity to TGFβ1 increased, but TGFβ production or TGFβ receptor expression was not altered. Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGFβ under anchorage-independent, but not anchorage-dependent, conditions without affecting TGFβ production or receptor characteristics. Thus, modulation of TGFβ growth responsiveness in these normal and oncogene transformed human mammary epithelial cells apparently occurs at a level distal to TGFβ receptor binding and is not solely correlated to expression of transforming oncogenes. Further, modulation of TGFβ production is not an indicator of malignant transformation in this system.
AB - Transforming growth factors-β (TGFβ) are a family of closely related, ubiquitously expressed growth factors with the common properties of induction of growth inhibition and expression of differentiation-related markers in epithelial cells. We investigated the role of TGFβ1 in growth regulation of normal human mammary epithelial cells and in benzo(a)pyrene immortalized sublines further transformed by oncogenes in retroviral vectors. The normal cells were markedly growth inhibited by TGFβ1, produced TGFβ in a latent form, and expressed TGFβ receptors. In the immortalized cells, both TGFβ-induced growth inhibition and TGFβ receptor binding were reduced. With the single oncogenes v-Ha-ras, v-mos, and SV40 T, growth sensitivity to TGFβ1 increased, but TGFβ production or TGFβ receptor expression was not altered. Transformation to full malignancy by both SV40 T and v-Ha-ras led to escape from growth inhibition by TGFβ under anchorage-independent, but not anchorage-dependent, conditions without affecting TGFβ production or receptor characteristics. Thus, modulation of TGFβ growth responsiveness in these normal and oncogene transformed human mammary epithelial cells apparently occurs at a level distal to TGFβ receptor binding and is not solely correlated to expression of transforming oncogenes. Further, modulation of TGFβ production is not an indicator of malignant transformation in this system.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024310430&partnerID=8YFLogxK
M3 - Article
C2 - 2553252
AN - SCOPUS:0024310430
VL - 49
SP - 6269
EP - 6274
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 22
ER -