Involvement of pRB family in TGFβ-dependent epithelial cell hypertrophy

Harold A. Franch, Jerry W. Shay, Robert J. Alpern, Patricia A. Preisig

Research output: Contribution to journalArticle

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Abstract

Although renal hypertrophy is often associated with the progressive loss of renal function, the mechanism of hypertrophy is poorly understood. In both primary cultures of rabbit proximal tubules and NRK-52E cells (a renal epithelial cell line), transforming growth factor β1 (TGFβ) converted epidermal growth factor (EGF)-induced hyperplasia into hypertrophy. TGFβ did not affect EGF-induced increases in c-fos mRNA abundance or cyclin E protein abundance, but inhibited EGF-induced entry into S, G2, and M phases. EGF alone increased the amount of hyperphosphorylated (inactive) pRB; TGFβ blocked EGF-induced pRB phosphorylation, maintaining pRB in the active form. To determine the importance of active pRB in TGFβ-induced hypertrophy, NRK- 52E cells were infected with SV40 large T antigen (which inactivates pRB and related proteins and p53), HPV16 E6 (which degrades p53), HPV16 E7 (which binds and inactivates pRB and related proteins), or both HPV16 E6 and E7. In SV40 large T antigen expressing clones, the magnitude of EGF + TGFβ-induced hypertrophy was inhibited and was inversely related to the magnitude of SV40 large T antigen expression. In the HPV16-infected cells, EGF + TGFβ-induced hypertrophy was inhibited in E7- and E6E7-expressing, but not E6-expressing cells. These results suggest a requirement for active pRB in the development of EGF + TGFβ-induced renal epithelial cell hypertrophy. We suggest a model of renal cell hypertrophy mediated by EGF-induced entry into the cell cycle with TGFβ-induced blockade at G1/S, the latter due to maintained activity of pRB or a related protein.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalJournal of Cell Biology
Volume129
Issue number1
DOIs
StatePublished - Apr 1995

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Transforming Growth Factors
Epidermal Growth Factor
Hypertrophy
Epithelial Cells
Polyomavirus Transforming Antigens
Viral Tumor Antigens
Kidney
Proteins
Cyclin E
G2 Phase
S Phase
Cell Division
Hyperplasia
Cell Cycle
Clone Cells
Phosphorylation
Rabbits
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology

Cite this

Involvement of pRB family in TGFβ-dependent epithelial cell hypertrophy. / Franch, Harold A.; Shay, Jerry W.; Alpern, Robert J.; Preisig, Patricia A.

In: Journal of Cell Biology, Vol. 129, No. 1, 04.1995, p. 245-254.

Research output: Contribution to journalArticle

Franch, Harold A. ; Shay, Jerry W. ; Alpern, Robert J. ; Preisig, Patricia A. / Involvement of pRB family in TGFβ-dependent epithelial cell hypertrophy. In: Journal of Cell Biology. 1995 ; Vol. 129, No. 1. pp. 245-254.
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