Chemical compounds found in vegetables such as Brussels sprouts, cabbage, and cauliflower, along with a number of Asian herbs, show promise for stopping the spread of breast cancer. A Berkeley Lab scientist is now testing a theory as to how these compounds work.
Many of the different forms of breast cancer tumors, including those that spread the fastest, depend upon the hormone estrogen for growth and development. Tests have shown that naturally-occurring antiestrogen compounds can be effective treatments. These antiestrogens are quite varied in chemical structure and may act through a cellular receptor normally used to detect toxins in the cell. If the mechanism by which antiestrogens prevent cancer growth can be identified, it might be possible to synthesize safer and even more effective versions.
James Bartholomew, a biophysicist with the Structural Biology Division, working in collaboration with Leonard Bjeldanes of the UC Berkeley Department of Nutrition, is now in the process of examining approximately 100 antiestrogen compounds, many of which were imported from Asia, where successful herbal treatments of breast cancer have been reported. Bartholomew believes that the tumor-suppressing activity of the antiestrogens is controlled by a protein called AhR. This protein is a receptor inside the cell that binds with a drug, or some other type of introduced chemical, in order to metabolize it.
"Little attention has been focused on the possible mitigating role of widely occurring natural antiestrogens in breast cancer," says Bartholomew. "Certain indole derivatives, such as indolo carbazole (ICZ), which are produced from dietary vegetables and by bacterial metabolism in the gastrointestinal tract, show potent antiestrogenic activity in model systems and may be useful as cancer preventive agents."
Bartholomew and Bjeldanes are employing standard biochemical and immunological assays in combination with a series of special molecular biology techniques to assess the effects of AhR on the expression of estrogen-regulating genes that have been linked to breast tumor growth. AhR is known to bind to TCDD, the environmental toxin contained in Agent Orange, and experiments by Bjeldanes and others have shown that it also binds to ICZ.
"Our theory is that when AhR binds to ICZ or to TCDD, the effect is to suppress the growth of breast cancer tumors," Bartholomew says.
In the next round of experiments, he and Bjeldanes will work with a special set of cell lines that lack the AhR receptor. These cell lines, which were developed at Berkeley Lab for studies of the notorious breast carcinogen benzo[a]pyrene, will be used to study the role AhR plays in enabling ICZ to inhibit estrogen-dependent tumors.
"If we can identify the mechanism by which ICZ and other antiestrogen compounds suppress breast cancer tumors, we should be able to predict which of these compounds will work best," says Bartholomew. "An important element in this puzzle is undoubtedly the structure of these receptors when they have a bound chemical (called a ligand). It is probably this structural detail that determines whether the receptor-ligand complex controls one set of genes or another."
Another argument for understanding this mechanism is safety. Antiestrogens, like TCDD, induce the activity of P-450, a cytochrome in the liver that metabolizes chemicals into carcinogenic derivatives.
"You would not want to be a smoker and be on an antiestrogen therapy," says Bartholomew. "If you know the mechanism by which antiestrogens suppress tumors, it opens up the possibility that you can design a dietary regime which would inhibit the growth of new tumor cells without affecting the chemicals used to kill existing tumors."
CAPTION: Jim Bartholomew of the Structural Biology Division is studying antiestrogen compounds in search of a safe and effective treatment for breast cancer. Photo by Joe Moore
The talk will focus on factors that contribute to increased risk for heart disease and things that women can do to reduce risk for premature atherosclerosis. Forte's research focuses on the role of high density lipoproteins (HDL) in protection against premature cardiovascular disease.
Forte is a Fellow of the Arteriosclerosis Council of the American Heart Association; a member of the American Association for the Advancement of Science, American Society for Cell Biology, Northern California Electron Microscopy Society, and American Institute of Nutrition.
She is a member of a number of professional associations and groups, such as the Technical Advisory Group to the California State Office of Women's Health, and chair-elect of the Arteriosclerosis Council, AHA, and has received numerous awards. She also is the Laboratory Point of Contact for the DOE Review of Women's Programs.
The Lab joins 50 other sponsors on the map, which is designed to highlight the Bay Area as the "birthplace of biotechnology." Synergistic Designs will use this artwork in on-going promotional efforts for the next two years. The map and its sponsors are also featured on Synergistic Design's web site "Biospace," accessible at http://www.biospace.com. Berkeley Lab's Technology Transfer Department coordinated the Lab's inclusion in this profile-raising effort.
CAPTION: Berkeley Lab Director Charles Shank and Life Sciences Division Director Mina Bissell (first and third from left) received framed copies of the new Biotech Bay promotional map from Technology Transfer Department Head Cheryl Fragiadakis and TTD's Bruce Davies.
The Berkeley Lab Calendar is published biweekly here on the World Wide Web and in Currents by the Public Information Department. Employees can list a meeting, class, or event in the Calendar by using this submission form. The deadline for submissions is 5 p.m. on Monday in the week that Currents is published.
In addition to the events listed below, Berkeley Lab's Washington, D.C. Projects office is hosting a Science and Technology Seminars series.Scientific Conferences
Introduction to EH&S Safety at LBNL (EHS 010), 1 - 3:30 p.m., Bldg. 51-201.
Radiation Protection - Fundamentals (EHS 400), 2:30 - 5 p.m., Bldg. 51-201.
Mark Rosenberg, Russ Montello, and David Batzloff of the Information and Computing Sciences Division set up this experimental service for the approximately 370 users of cc:Mail here. Through the Web, they can now retrieve their mail as well as send new messages and delete old ones.
To log onto your cc:Mail account through the Web, use the address http://www-ccmail.lbl.gov. When you have finished using cc:Mail, remember to log out before navigating elsewhere on the Web.
'85 ISUZU Trooper, 108K mi., a/c, p/s, 4WD, $3600. Bill, X4686, 601-1404
'85 NISSAN Sentra, 2-dr, 100K mi., AM/FM cass., a/c, 5-spd, new clutch & tires, exc. cond., 2nd owner, $2200. Javier, X5446, 843-9534
'86 VW GTI, sunrf, leather, sports pkg., new muffler, battery, smog & tires, $3800. 528-3575
'87 CHEVY Nova, a Toyota Corolla clone built in Fremont, blue, 4-dr, a/c, 5-spd, 108K mi., orig. owner, exc. cond., $2700. Michael, X5650, 947-1111
'87 FORD/MERCURY Lynx, needs clutch & battery, gd engine & tires, 70K mi., $800/b.o. 635-4417 (after 6 p.m.)
'87 TOYOTA Tercel, 114K mi., hatchbk, seats torn, runs great, $2400/b.o. Jurgen, X7843, 528-3151
MOTORCYCLE, '82 Yamaha Seca 650, exc. cond., $1800. Judy, X6540, 631-6642
VANPOOL, riders wanted from Rohnert Park - stopping at Petaluma & Novato - ending at Berkeley BART, Commuter Checks accepted. Shirley, X4521
SUMMER JOB for Swiss high school student, graduating in June, baby-sitter/mother's helper, exp. w/children. 527-0992, 527-3664 (FAX)
COMPUTER, Lap Top Acernote 786, 8M Ram 500MB HD 486DX4/75, 256 color display, 2 card slots, trackball, many programs installed, orig. box & manuals, exc. cond., $1500/b.o. 235-3983
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CRIB, Childcraft, med. oak finish, single drop side, exc. cond., crib mattress, Evenflo, exc. cond., clean, used for 1 child, $100 for both. X7130
EXERCISE MACHINE, Healthrider, brand new, never used, $275. Alan, 234-9041
FREE-STANDING HEATER, Schwank-Perfection, model VC2500TN-R, 50K BTU, used twice, exc. cond., $450. Denny, 237-8171
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LOFT BED KIT, all pine wood, bolted construction, never used, $125/b.o. Stan, X6849, 845-7468
MOVING SALE, Windsurfer One Design, complete, fair cond., $30; waxable X-country skis & poles, $20; queen sz. waterbed w/heater, sheets etc., $20. Kathy, X4383, 986-0323 (eve.)
MOVING SALE, 2 armchairs, $20 ea.; 2 coffee tables, $40; Sony stereo, $150 & other things. Anders, X4601, 526-3374
MOVING SALE, full sz. futon, TV, tables, chairs, iron, shelves, kitchen appliances & more. Javier, X5446, 843-9534
NORDIC TRACK, Basic Skier, incl. distance/spd meter, hardly used, $150. Carol, 637-1814
ORGAN, console, Yamaha, walnut cabinet, 8 rhythm settings, $200. Monte, X6761
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PERSIAN RUG, antique, 60 yrs. in family, perfect cond., hand-knotted Hammedan, 5'x7', predominately red/multi., $600/b.o. 883-1652
RECEIVERS, stereo-surround, Denon-AVR1000, $275; Sony, 6X808ES, $300; Onkyo, TX-SV727, $450; CD player, Technics, 5 disc changer, $100. Mark, X6825
SAILBOATS (2), 22' Columbia fiberglass w/fin keel, sails, 7.5 HP outboard engine, toilet & galley, slps 4, $2K; Mystic 24' w/full keel, sails, 4 cyl. atomic gas inboard engine, standing headroom, toilet & galley, slps 4, $3K. Nan, 527-4298
WEIGHT TRAINING MACHINE, BMI Model 9800, exc. cond., new cables, $110. Dick, X6466, 526-6087
BERKELEY, Northside, 2417 Hilgard, unfurn. 1-bdrm apt in a 4 unit bldg, frpl, hardwd flrs, walking distance to UCB, nr bus, shops, cafes & restaurants, mo.-to-mo. rental, incl. water & garbage. 524-5583
BERKELEY, 2 rms avail. in furn. home, nr UCB & Rose Garden, washer/dryer, views, frpl, hot tub, decks, $450 & $500/mo. David, 525-4470
BERKELEY HILLS, Euclid/Cedar, 5 blks from UCB, furn. rm in pvt. home, kitchen privs., washer/dryer, deck, bay views, nr trans., shops, tennis cts & Rose Garden, no smoking, no pets, $450/mo. + util. 548-1287
CASTRO VALLEY, 2 bdrms avail. in home, one w/pvt bth, laundry & kitchen privs, short/long term, rent + dep. negot. Marek, X5029, 582-5867
EL CERRITO, furn. 2-bdrm townhouse, 1-1/2 bth, 2-car garage, washer/dryer, inner courtyard nr swimming pool, avail. 4/1-9/30, $850/mo. 525-2135
KENSINGTON, furn. 3-bdrm house, lg. garden, 1 cat, avail. 5/1 for duration of summer, $1200-$1300/mo. depending upon sz. of family. Ruth, 526-2007
OAKLAND, nr Mormon Temple, 2-bdrm house, share bathrm during weekdays, prefer female, $700/mo. + dep. 531-2058 (msg.)
RICHMOND (off Arlington), unfurn. 3-bdrm, 1-bth house, partial view of bay, frpl, W/D hook-ups, garage, hardwd flrs, refrig., stove, yd, nr bus & BART, 1 yr lease, $1200/mo + 1 mo. dep., availability negot. Dee, 235-6587 (eve.)
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UPPER ROCKRIDGE, 4 mi. from UC, furn. 3-bdrm home, yd, nr exc. schools, no smoking, no pets, avail. 8/1 for 1 yr. (sabbatical), car option avail., $1750/mo. 655-7674
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WANTED: 3-bdrm house in Orinda/Moraga/Lafayette general area, from end of Aug. for 1 yr., for visiting scientist from Korea, wife & 2 children (6th & 8th grades), prefer furn. Bertha/Donald, 642-9345
WANTED: Albany/Kensington, 3-bdrm house for 1 yr. lease, 1500 sq. ft. or larger. Alan, 234-9041
WANTED: visiting French scientist, spouse & 3 children, want to exchange 4-bdrm apt in center Paris for house near LBNL starting 6/20 until end of Aug., car exchange also possible. 33 1 43389440 (France), email@example.com
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