The overall objective of this research is to define the role of estrogen-induced uterine-, kidney- and pituitary tumor-derived growth factors in the proliferation of rat pituitary tumor cells in vivo and in vitro. The rat pituitary tumor lines to be used in these studies are the GH3/C14 and GH?9?C?1? cells. Our studies with these lines have shown that estrogens are required for optimal growth in vivo but are not capable of promoting continuous growth of these cells in vitro. We have considered several possible explanations for these observations in culture; however, our most recent approach has been to ask whether the mitogenic role of estrogens in vivo may be mediated by steroid hormone control of the production and secretion of growth factors specific for the hormone-responsive pituitary tumor cells. To evaluate the possibility of a mediated mechanism involving estrogen-induced polypeptide growth factor, we first prepared extracts of tissues removed from estrogen-treated and estrogen-deficient animals and assayed for growth activity by addition of extracts to cells in serum-free medium. Our experiments demonstrate that estrogens elevate the levels of growth factors for GH3/ C15 pituitary cells in extracts of both rat uterine and rat kidney tissue. We have now purified pituitary tumor cell growth factors from lyophilized powders of sheep uteri and kidneys. These activities are related, but not identical, polypeptides of Mr = 4,200. These properties are now under further investigation. In addition, autocrine/parocrine growth factor (Mr 70,000) have been identified in pituitary tumors. To date, our experiments suggest a model of hormone-responsive pituitary tumor growth in vivo that includes a mechanism that involves uterus, kidney, and an autocrime mechanism of tumors producing specific polypeptide growth factors locally within estrogenresponsive and autonomous tumors. (D)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026617-08
Application #
3167383
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-07-01
Project End
1988-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Karey, K P; Sirbasku, D A (1989) Glutaraldehyde fixation increases retention of low molecular weight proteins (growth factors) transferred to nylon membranes for western blot analysis. Anal Biochem 178:255-9
Riss, T L; Sirbasku, D A (1989) Identification of a 15,000-molecular-weight form of immunoreactive transforming growth factor alpha in extracts of porcine pituitary. J Cell Physiol 138:393-404
Riss, T L; Stewart, B H; Sirbasku, D A (1989) Rat pituitary tumor cells in serum-free culture. I. Selection of thyroid hormone-responsive and autonomous cells. In Vitro Cell Dev Biol 25:127-35
Riss, T L; Sirbasku, D A (1989) Characterization of polyclonal antibodies that distinguish acidic and basic fibroblast growth factors by using western immunoblotting and enzyme-linked immunosorbent assays. J Cell Physiol 138:405-14
Ogasawara, M; Karey, K P; Marquardt, H et al. (1989) Identification and purification of truncated insulin-like growth factor I from porcine uterus. Evidence for high biological potency. Biochemistry 28:2710-21
Riss, T L; Sirbasku, D A (1989) Rat pituitary tumor cells in serum-free culture. II. Serum factor and thyroid hormone requirements for estrogen-responsive growth. In Vitro Cell Dev Biol 25:136-42
Ogasawara, M; Sirbasku, D A (1988) A new serum-free method of measuring growth factor activities for human breast cancer cells in culture. In Vitro Cell Dev Biol 24:911-20
Danielpour, D; Riss, T L; Ogasawara, M et al. (1988) Growth of MTW9/PL2 estrogen-responsive rat mammary tumor cells in hormonally defined serum-free media. In Vitro Cell Dev Biol 24:42-52
Karey, K P; Sirbasku, D A (1988) Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol. Cancer Res 48:4083-92
Riss, T L; Sirbasku, D A (1987) Purification and identification of transferrin as a major pituitary-derived mitogen for MTW9/PL2 rat mammary tumor cells. In Vitro Cell Dev Biol 23:841-9

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